The effect of elemene on lung adenocarcinoma A549 cell radiosensitivity and elucidation of its mechanism

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Five-year OS of chronic myeloid leukemia patients treated with a 3rd tyrosine kinase inhibitor according to disease phase." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Beatriz Felicio Ribeiro, Eliana C M Miranda, Dulcinéia Martins de Albuquerque, Márcia T Delamain, Gislaine Oliveira-Duarte, Maria Helena Almeida, Bruna Vergílio, Rosana Antunes da Silveira, Vagner Oliveira-Duarte, Irene Lorand-Metze, Carmino A De Souza, Katia B B Pagnano" "autores" => array:12 [ 0 => array:2 [ "nombre" => "Beatriz Felicio" "apellidos" => "Ribeiro" ] 1 => array:2 [ "nombre" => "Eliana C M" "apellidos" => "Miranda" ] 2 => array:2 [ "nombre" => "Dulcinéia Martins" "apellidos" => "de Albuquerque" ] 3 => array:2 [ "nombre" => "Márcia T" "apellidos" => "Delamain" ] 4 => array:2 [ "nombre" => "Gislaine" "apellidos" => "Oliveira-Duarte" ] 5 => array:2 [ "nombre" => "Maria Helena" "apellidos" => "Almeida" ] 6 => array:2 [ "nombre" => "Bruna" "apellidos" => "Vergílio" ] 7 => array:2 [ "nombre" => "Rosana Antunes" "apellidos" => "da Silveira" ] 8 => array:2 [ "nombre" => "Vagner" "apellidos" => "Oliveira-Duarte" ] 9 => array:2 [ "nombre" => "Irene" "apellidos" => "Lorand-Metze" ] 10 => array:2 [ "nombre" => "Carmino A" "apellidos" => "De Souza" ] 11 => array:2 [ "nombre" => "Katia B B" "apellidos" => "Pagnano" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222013461?idApp=UINPBA00004N" "url" => "/18075932/0000007000000008/v1_202212011321/S1807593222013461/v1_202212011321/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "CLINICAL SCIENCE" "titulo" => "The effect of elemene on lung adenocarcinoma A549 cell radiosensitivity and elucidation of its mechanism" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "556" "paginaFinal" => "562" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Kun Zou, Caigang Liu, Zhuo Zhang, Lijuan Zou" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Kun" "apellidos" => "Zou" ] 1 => array:2 [ "nombre" => "Caigang" "apellidos" => "Liu" ] 2 => array:4 [ "nombre" => "Zhuo" "apellidos" => "Zhang" "email" => array:1 [ 0 => "799832582@qq.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] 3 => array:4 [ "nombre" => "Lijuan" "apellidos" => "Zou" "email" => array:1 [ 0 => "zoulijuanfl@163.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "2nd Affiliated Hospital of Dalian Medical University, Radiotherapy Department, Dalian/Liaoning, China" "identificador" => "aff1" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Corresponding author:" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig4" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 973 "Ancho" => 780 "Tamanyo" => 88632 ] ] "descripcion" => array:1 [ "en" => "Western blot analysis of the protein levels of Bcl-2, p53 and DNA-PKcs. A549 cells were irradiated with 4 Gy X-rays following treatment with 10 or 20 μg/mL elemene for 24 h. Proteins were extracted and separated by SDS-PAGE. (A) Levels of Bcl-2, p53 and DNA-PKcs were quantitated by densitometry, and the ratios of the three proteins are displayed. Values represent the mean ± SD, n=3, **p<0.01 compared to the control, ##p<0.01 compared to radiation alone. Elemene inhibited the protein expression of (B) DNA-PKcs and (C) Bcl-2 and promoted the protein expression of p53. Key: 1, Control; 2, irradiation; 3, 10 μg/mL; 4, 20 μg/mL; 5, 10 μg/mL + irradiation; 6, 20 μg/mL + irradiation." ] ] ] "textoCompleto" => "INTRODUCTIONLung cancer is one of the most common malignant tumors, and radiotherapy is the prevailing method of choice for treatment <a class="elsevierStyleCrossRef" href="#bib1">1</a>, especially for middle- to late-stage lung cancer. Radiation works by damaging the DNA of cancerous cells and altering apoptosis-related genes or proteins, leading to cell death. Improving the radiosensitivity of tumor cells is a significant factor that would improve the efficacy of radiotherapy.DNA-dependent protein kinase (DNA-PK) is an important enzyme that participates in DNA damage repair and has become the main target of radiation sensitivity interventions <a class="elsevierStyleCrossRef" href="#bib2">2</a>–<a class="elsevierStyleCrossRef" href="#bib4">4</a>. The catalytic subunit (cs) of DNA-PK affects cellular radiosensitivity by regulating the phosphorylation of DNA damage repair-related proteins <a class="elsevierStyleCrossRef" href="#bib5">5</a>. Thus, inhibition of DNA-PKcs gene expression can block DNA double-strand break (DSB) repair and improve cellular radiosensitivity.Cellular apoptosis is the core characteristic of radiotherapy, and regulation of this process thus plays an important role in cellular radiosensitivity <a class="elsevierStyleCrossRef" href="#bib6">6</a>,<a class="elsevierStyleCrossRef" href="#bib7">7</a>. Previous studies have shown that apoptosis-related genes, such as phosphoprotein (p53), p16, B-cell lymphoma-2 (Bcl-2), and erythroblastic leukemia viral oncogene homolog 2 (erbB-2), are associated with tumor radiosensitivity <a class="elsevierStyleCrossRef" href="#bib8">8</a>,<a class="elsevierStyleCrossRef" href="#bib9">9</a>, especially p53 and Bcl-2. It has also been reported that elemene interacts with the frontier orbitals of DNA bases to form complexes between DNA molecules. Specifically, Jiang et al. <a class="elsevierStyleCrossRef" href="#bib10">10</a> showed that elemene increases the radiosensitivity of A549 cells, the mechanism for which may be related to the upregulation of p53, downregulation of Bcl-2, and induction of cellular apoptosis.Elemene, which is extracted from Zingiberaceae plants (Curcuma aromatica Salisb.), is a non-cytotoxic antitumor compound that can improve the radiosensitivity of tumor cells <a class="elsevierStyleCrossRef" href="#bib11">11</a>. Results of an in vitro study showed that elemene increased the radiosensitivity of renal carcinoma cells, tongue squamous cancer cells, and non-small cell lung cancer cells <a class="elsevierStyleCrossRef" href="#bib10">10</a>,<a class="elsevierStyleCrossRef" href="#bib12">12</a>,<a class="elsevierStyleCrossRef" href="#bib13">13</a>. Animal experiments further showed that elemene exhibited radiotherapy-sensitizing effects in many types of tumor cells, such as transplanted murine U14 tumors, kidney cancer GRC-1 cells, and tongue squamous carcinoma Tca-8113 cells <a class="elsevierStyleCrossRef" href="#bib13">13</a>–<a class="elsevierStyleCrossRef" href="#bib15">15</a>. In addition, beta elemene enhances A549 cell radiosensitivity through enhancement of DNA damage and suppression of DNA repair <a class="elsevierStyleCrossRef" href="#bib16">16</a>.In the current study, A549 cells were irradiated following elemene treatment, and the changes in expression of the apoptosis-related genes Bcl-2 and p53 as well as the double-stranded DNA damage repair-related gene DNA-PKcs were evaluated. These experiments were conducted to further understand elemene's molecular mechanism of action in enhancing radiation sensitivity of A549 cells.MATERIALS AND METHODSCell cultureThe human lung adenocarcinoma A549 cell line was purchased from the Chinese Academy of Medical Sciences (CAMS) Cell Center and passaged at the Second Affiliated Hospital of Dalian Medical University Center Laboratory. The cells were cultured in RPMI 1640 medium containing 10% inactivated fetal bovine serum (FBS) at 37°C under an atmosphere of 5% CO2 and saturated humidity. The cells were subcultured when they reached the exponential phase.Reagents and instrumentsElemene (0.1 g/20 mL), which was obtained from DaLian JinGang Pharmaceutical Co. Ltd. (China), was dissolved in RPMI 1640 medium to final working concentrations of 10 and 20 µg/mL before use. RPMI 1640 medium was obtained from Gibco (USA); FBS was obtained from TianJin TBD Biotechnology Company (China); p53 and Bcl-2 antibodies were obtained from Santa Cruz (USA, 1:1,000); and DNA-PKcs antibody (1:2,000), anti-human β-actin mouse monoclonal antibody and histone H1 internuclear internal reference antibodies (1:200) were obtained from Neomarker (USA). The Jim-X half-dry transfer electrophoresis apparatus was obtained from DaLian JingMai Biotechnology Co. Ltd. (China). The flow cytometer was purchased from the Gene Company (USA). The CK2 type inverted microscope was obtained from Olympus (Japan). The BX51 type fluorescent microscope was also obtained from Olympus (Japan).Irradiation conditionsCell irradiation was performed using the Varian 2300C/D medical linear accelerator (Varian Companies, USA) with a coverage field of 20 cm × 20 cm. The culture dish was placed in the radiation field above 1.5 cm of organic glass. Cells with irradiated with 6 MV X-ray irradiation at a dosage rate of 300 cGy/min, a rack angle of 180°, and source-to-surface distance (SSD) of 100 cm.Clonogenic assayLogarithmic-growth phase cells were inoculated in a 60-mm culture dish. After adherence, the cells in the drug and combined irradiation groups were cultured in the presence of 10 or 20 μg/mL elemene and seeded in culture plates at 100 cells/well for 24 h. The cells were exposed to 0, 2, 4, 6, 8, and 10 Gy of irradiation and cultured for another 14 days. The number of cell clones viewed under a low magnification microscope was 50. The plating efficiency (PE) was calculated relative to the control group (0 Gy), and the survival fraction (SF) of each group was calculated as follows: SER=control group (D0, Dq)/experimental group (D0, Dq).Morphological assessment of apoptosisThe cells were treated as follows: the control group received RPMI 1640 medium; the radiation group received a radiation dose of 4 Gy; the drug group was treated with 10 or 20 µg/mL elemene; and the drug plus radiation group was treated with 10 or 20 µg/mL elemene followed by a radiation dose of 4 Gy. Following incubation with elemene, the exponentially growing cells were irradiated as described above. Samples of 3 × 105 cells were then collected from each group, treated with pancreatic enzyme digesting cells, rinsed twice with PBS, and centrifuged at 1,000 rpm for 5 min. The SF was determined using the following equation: SF=colony number/(plating cell number × PE).The dose survival curve was fitted using the linear-quadratic (LQ) function model S=e-(αd+βd2) <a class="elsevierStyleCrossRef" href="#bib17">17</a> for calculating radiobiological parameters, including the sensitivity enhancement ratio (SER), SER of the mean lethal dose (D0) SERDq, and SER of the quasi-threshold dose (Dq) SERD0. Nuclear morphology was examined using fluorescence microscopy following Hoechst 33342 staining (final concentration 8 mg/mL) for 15 min at 37°C. Imaging was performed using an Olympus BX-51 fluorescent microscope with appropriate filter cubes. The excitation and emission wavelengths were 350 nm 460 nm, respectively.Apoptosis standardNormal cells demonstrated uniform dispersion of low-density fluorescence, while apoptotic cells showed high-density fluorescence, characterized by a bright blue hue.Assessment of apoptosisThe cells used were grouped and treated as specified above. Then, samples of 3 × 105 cells were collected from each group, treated with pancreatic enzyme digesting cells, rinsed twice with PBS, and centrifuged at 1,000 rpm for 5 min. The cells were treated with 100 μL 2% Triton X-100 for 20 min, rinsed twice with PBS, and centrifuged at 1,000 rpm for 5 min. Next, 200 μL of DNA-Prep LPR reagent (Beckman-Coulter Ltd) was added for 20 min, and the cells were rinsed twice with PBS, followed by centrifugation at 1,000 rpm for 5 min. The cells were resuspended in PBS and 50 µg/mL propidium iodide (PI) reagent containing 480 μL of PBS, 5 μL of PI (5 mg /mL), and 5 μL of RNase (10 mg /mL), and 10 μL of Triton X-100 (10%) was added 30 s later. Single-cell suspensions were analyzed by flow cytometry to determine the cellular apoptosis rate.Neutral comet assayA549 cells were irradiated in the absence or presence of elemene (10 or 20 µg/mL) and assayed immediately after radiation or returned to the incubator for 24 h to permit repair. The comet assays were performed immediately after incubation with elemene, irradiation or combination treatment. Tumor cells were grown on glass microscope slides using a standard protocol <a class="elsevierStyleCrossRef" href="#bib18">18</a>. The slides were submerged in lysing solution containing 30 mM ethylenediaminetetraacetic acid (EDTA) and 0.5% sodium dodecyl sulfate (SDS, pH 8.3) for 1.5 h at 37°C. Following lysis, the slides were rinsed three times in Tris-borate-EDTA (TBE) buffer consisting of 90 mM Tris, 90 mM boric acid, and 2 mM EDTA, pH 8.5, and stored overnight in TBE buffer at 4°C. Slides were transferred to an electrophoresis unit with TBE buffer and electrophoresed at 1 V/cm for 20 min. Following electrophoresis, the slides were neutralized with 0.4 M Tris buffer (pH 7.5) and stained with ethidium bromide (20 µg/mL). Finally, the slides were viewed using an Olympus BX‐51 fluorescent microscope (excitation filter 549 nm, barrier filter 590 nm). Images of 50 randomly selected cells from each slide were analyzed with Comet Assay Software Project casp‐1.2.2 (University of Wroclaw, Poland). The tail moment was used as a parameter to assess DNA damage. The assay was completed three separate times, and 50 cells were evaluated per experiment.Western blot assayWestern blotting was performed to detect the expression levels of DNA-PKcs, p53, and Bcl-2. The cells were grouped and treated as specified above. After 24 h, western blot analysis was performed using cytosolic fractions as previously described <a class="elsevierStyleCrossRef" href="#bib19">19</a>. Equal amounts of cytosolic protein were separated on 8–12% SDS polyacrylamide denaturing gels and transferred to nitrocellulose membranes. The membranes were blocked in TBS-Tween (TBS-T, 10 mM Tris-HCl, pH 7.4; 150 mM NaCl; and 0.1% Tween-20) with 5% non-fat milk for 2 h and incubated with specific primary antibodies overnight at 4°C. Finally, the membranes were incubated with horseradish peroxidase (HRP)-conjugated secondary antibodies at 37°C for 2 h and assayed using an enhanced chemiluminescence plus detection system.Statistical analysisData were analyzed using the statistical package for the social sciences (SPSS) v13.0 software. Data are expressed as the mean ± standard deviation (SD). The statistical significance of differences between groups was determined by one-way analysis of variance (ANOVA), followed by post hoc analysis using the least significant difference (LSD) for multiple comparisons. The Spearman test was used for the correlation analysis of the relationships between the expression levels of genes. The level of significance was set at p<0.05 and p<0.01 for all statistical analysis.RESULTSEffects of elemene on cell radiosensitivityThe survival fraction of A549 cells decreased following treatment with different doses of radiation and the same concentration of elemene. Conversely, the A549 cell survival fraction decreased in the groups treated with the same dose of radiation in combination with increasing concentrations of elemene (<a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>). Following treatment with 10 or 20 μg/mL elemene, the A549 cell survival curve shifted to the left, the shoulder area was diminished, and the steepness of the curve increased (<a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>). Based on the cell survival curve, the radiobiological parameters and radiosensitization ratio were obtained and are listed in <a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>. These data show that, compared with the control group, the SERD0 and SERDq values for the 10 and 20 μg/mL elemene treatment groups were greater than 1. Furthermore, the ratio gradually increased with an increasing drug concentration (<a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>).<elsevierMultimedia ident="tbl1"></elsevierMultimedia><elsevierMultimedia ident="fig1"></elsevierMultimedia><elsevierMultimedia ident="tbl2"></elsevierMultimedia>Effect of elemene on A549 cell apoptosisFluorescence microscopy showed that compared with the control group, the groups treated with radiation alone and elemene alone contained more apoptotic cells (<a class="elsevierStyleCrossRef" href="#fig2">Figure 2</a>). Furthermore, significantly higher apoptotic levels were observed in the groups treated with radiation and elemene at 10 or 20 μg/mL (<a class="elsevierStyleCrossRef" href="#fig2">Figure 2A</a>). Flow cytometry revealed that compared with the control group, the apoptosis rate of the group treated with radiation alone appeared to increase, but this was not found to be statistically significant (p>0.05). The apoptosis rate of the group treated with elemene alone did not change (p>0.05), while the apoptosis rate of the elemene plus radiation group increased significantly (p<0.01). The rate of apoptosis increased with increasing concentrations of elemene (<a class="elsevierStyleCrossRef" href="#fig2">Figure 2B</a>).<elsevierMultimedia ident="fig2"></elsevierMultimedia>Effect of elemene on DSB repair in A549 cells<a class="elsevierStyleCrossRef" href="#fig3">Figure 3</a> (0 h) shows that both elemene and irradiation alone increased the tail intensity in A549 cells, and the degree of DSB was augmented as the elemene concentration increased. In particular, the results showed a higher number of DSB in the combination group than the irradiation alone and elemene alone groups (p<0.01). As shown in <a class="elsevierStyleCrossRef" href="#fig3">Figure 3</a> (24 h), following incubation for 24 h, the tail intensity in the irradiation alone group returned to background levels, while there was a significant increase in the amount of remaining tail intensity in the combination group compared with the irradiation alone and elemene alone groups (p<0.01).<elsevierMultimedia ident="fig3"></elsevierMultimedia>Effects of elemene on DNA-PKcs, Bcl-2, and p53 protein expression in A549 cellsThe results shown in <a class="elsevierStyleCrossRef" href="#fig4">Figure 4A</a> revealed that in the 10 and 20 μg/mL combined treatment groups, a significant decrease in the protein expression of DNA-PKcs (p<0.01, <a class="elsevierStyleCrossRef" href="#fig4">Figure 4B</a>) and Bcl-2 (p<0.01, <a class="elsevierStyleCrossRef" href="#fig4">Figure 4C</a>) was observed, while the p53 protein expression level was significantly increased (p<0.01, <a class="elsevierStyleCrossRef" href="#fig4">Figure 4C</a>).<elsevierMultimedia ident="fig4"></elsevierMultimedia>Protein expression correlation analysisSpearman correlation analysis showed that DNA-PKcs and p53 protein expression was negatively correlated (r=-0.569, p<0.05), while DNA-PKcs expression was positively correlated with Bcl-2 protein expression (r=0.755, p<0.05).DISCUSSIONBasic research in radiation biology has shown that radiation therapy works mainly by damaging tumor cell DNA and altering the expression of apoptosis-related genes and proteins. The radiosensitivity of tumor cells relates to their capacity to repair DSB via the related genes DNA-PKcs, Ku70/80, and ataxia telangiectasia mutated (ATM). Other genes known to be involved in radiosensitivity and responsible for apoptosis regulation include p53, Bcl-2, c-myc proto-oncogene (c-myc), and survivin <a class="elsevierStyleCrossRef" href="#bib9">9</a>. Beta elemene, which is the active component of elemene, has recently been demonstrated to enhance the radiosensitivity of human cancer cell lines in vitro and in an animal tumor model in vivo<a class="elsevierStyleCrossRef" href="#bib16">16</a>,<a class="elsevierStyleCrossRef" href="#bib20">20</a>. In particular, beta elemene was found to enhance radiosensitivity by influencing the cell cycle distribution of gastric cancer MKN28 cells, and the mechanisms responsible for this effect include the induction of G2/M phase arrest, inhibition of sublethal damage repair, and induction of cell apoptosis, which enhances the killing effects of radioactive rays <a class="elsevierStyleCrossRef" href="#bib21">21</a>. The results of the current study show that the SERD0 and SERDq values of A549 cells exposed to a low concentration of cytotoxic elemene were greater than 1. In addition, elemene enhanced the sensitivity of A549 cells to radiotherapy. Cellular apoptosis is fundamental to radiotherapy, and its regulatory mechanism plays an important role in cellular radiosensitivity. Apoptosis-related genes such as p53 and Bcl-2 have important regulatory functions in the progression of rapid apoptosis induced by radiation therapy. For instance, a previous study showed that the levels of the antiapoptotic genes Bcl-2 and Bcl-xl in A549 cells decreased, while p53 expression and the production of exosomes increased, following elemene treatment <a class="elsevierStyleCrossRef" href="#bib22">22</a>. This result demonstrates that both p53 and Bcl-2 have important regulatory actions in cervical cancer cell apoptosis induced by radiation. A number of experimental studies have further shown that elemene is involved in regulating the expression of Bax, c-myc, p53, poly (ADP-ribose) polymerase (PARP), survivin, and livin as well as inducing tumor cell apoptosis <a class="elsevierStyleCrossRef" href="#bib23">23</a>–<a class="elsevierStyleCrossRef" href="#bib26">26</a>. Our results showed that, compared with the exposure alone group, the group that received elemene combined with irradiation exhibited increased p53 gene expression and significantly decreased Bcl-2 gene expression, and the expression of both genes was significantly correlated. Furthermore, elemene was shown to regulate expression of the apoptosis-related genes Bcl-2 and p53 and induce A549 cell apoptosis, thereby increasing cell radiosensitivity.Interestingly, when Bcl-2 and p53 gene expression was significantly altered, DNA-PKcs protein expression was significantly decreased in the combined treatment group. This result indicates that elemene is also involved in regulating DNA damage repair pathways. Protein kinase activation leads to the phosphorylation of downstream DNA repair proteins, which initiate DNA chain fracture repair <a class="elsevierStyleCrossRef" href="#bib27">27</a>, and the relationship between DNA-PKcs and radiotherapy sensitivity has been a topic of significant research in recent years. It is well established that inhibiting tumor cell expression of DNA-PKcs increases radiation sensitivity. Panet al. <a class="elsevierStyleCrossRef" href="#bib28">28</a> studied the relationship between DNA-PKcs expression and radiation sensitivity in non-small cell lung cancer cell lines, and in adenocarcinomas and large cell carcinomas, DNA-PKcs was shown to be an important component regulating cellular radiosensitivity. This result indicates that DNA-PKcs may be predictive of non-small cell lung cancer cell radiosensitivity. Zou et al. <a class="elsevierStyleCrossRef" href="#bib29">29</a> silenced the DNA-PKcs gene of human mammary epithelial cells (MCF10F) using small interfering RNA (siRNA) technology. Simultaneously, the expression of DNA repair-related proteins, such as DNA-PKcs, Ku80, ATM, and p53, was decreased in these cells, while their sensitivity increased with low doses of radiation. Small molecule inhibitors of DNA-PKcs were also shown to enhance radiation sensitivity of cervical cancer cells <a class="elsevierStyleCrossRef" href="#bib30">30</a>. Our experimental results showed that elemene inhibited DNA-PKcs expression in A549 cells, reduced DNA damage repair, and increased cellular radiosensitivity.DNA-PKcs is a protein with a wide range of functions and is involved in DNA damage repair, apoptosis, and V(D)J recombination <a class="elsevierStyleCrossRef" href="#bib31">31</a>. Yu et al. <a class="elsevierStyleCrossRef" href="#bib32">32</a> found that in non-small cell lung cancer, high expression of DNA-PKcs increased the activity of the DNA damage repair system. In addition, apoptosis inhibition caused by mutant p53 and Bcl-2 expression exhibited a combined effect, which may explain the development of resistance to radiotherapy in small-cell lung cancer. Daido et al. <a class="elsevierStyleCrossRef" href="#bib33">33</a> indicated that following exposure to low doses of radiation, human malignant glioma M059J cells that lack DNA-PKcs underwent massive autophagic cell death that was significantly increased after exposure to DNA-PKcs inhibitors. Furthermore, DNA-PKcs inhibitors exert radiotherapy-sensitizing effects on glioma cells by enhancing type II programmed cell death. Lee et al. <a class="elsevierStyleCrossRef" href="#bib34">34</a> found that p53-inducible gene 3 (PIG3) is involved in apoptosis caused by p53 activation and that this molecule can regulate DNA-PKcs expression. Moreover, knockdown of PIG3 was shown to decrease the level of DNA-PKcs in cells. Our study further addressed the correlation between DNA-PKcs, Bcl-2, and p53 expression, and the results showed that DNA-PKcs expression was significantly positively correlated with that of Bcl-2 (r=0.755, p<0.05) and significantly negatively correlated with p53 (r=0.569, p<0.05). We further showed that DNA-PKcs was closely related to apoptosis and that elemene increased apoptosis of A549 cells and strengthened cellular radiosensitivity by inhibiting DNA-PKcs expression.In summary, elemene exhibits radiotherapy-sensitizing effects on lung adenocarcinoma A549 cells, and its mechanism of action involves the upregulation of p53 and downregulation of Bcl-2 to promote cell apoptosis, as well as the downregulation of DNA-PKcs to inhibit DSB repair. However, the specific mechanism of action of elemene requires further elucidation.AUTHOR CONTRIBUTIONSZou K, Zhang Z and Zou L designed the research study and wrote the paper. Zou K and Liu C performed the research. Zou K and Zhang Z analyzed the data." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "xpalclavsec1582180" "titulo" => "KEYWORDS" ] 1 => array:2 [ "identificador" => "cesec10" "titulo" => "INTRODUCTION" ] 2 => array:3 [ "identificador" => "cesec20" "titulo" => "MATERIALS AND METHODS" "secciones" => array:10 [ 0 => array:2 [ "identificador" => "cesec30" "titulo" => "Cell culture" ] 1 => array:2 [ "identificador" => "cesec40" "titulo" => "Reagents and instruments" ] 2 => array:2 [ "identificador" => "cesec50" "titulo" => "Irradiation conditions" ] 3 => array:2 [ "identificador" => "cesec60" "titulo" => "Clonogenic assay" ] 4 => array:2 [ "identificador" => "cesec70" "titulo" => "Morphological assessment of apoptosis" ] 5 => array:2 [ "identificador" => "cesec80" "titulo" => "Apoptosis standard" ] 6 => array:2 [ "identificador" => "cesec90" "titulo" => "Assessment of apoptosis" ] 7 => array:2 [ "identificador" => "cesec100" "titulo" => "Neutral comet assay" ] 8 => array:2 [ "identificador" => "cesec110" "titulo" => "Western blot assay" ] 9 => array:2 [ "identificador" => "cesec120" "titulo" => "Statistical analysis" ] ] ] 3 => array:3 [ "identificador" => "cesec130" "titulo" => "RESULTS" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "cesec140" "titulo" => "Effects of elemene on cell radiosensitivity" ] 1 => array:2 [ "identificador" => "cesec150" "titulo" => "Effect of elemene on A549 cell apoptosis" ] 2 => array:2 [ "identificador" => "cesec160" "titulo" => "Effect of elemene on DSB repair in A549 cells" ] 3 => array:2 [ "identificador" => "cesec170" "titulo" => "Effects of elemene on DNA-PKcs, Bcl-2, and p53 protein expression in A549 cells" ] 4 => array:2 [ "identificador" => "cesec180" "titulo" => "Protein expression correlation analysis" ] ] ] 4 => array:2 [ "identificador" => "cesec190" "titulo" => "DISCUSSION" ] 5 => array:2 [ "identificador" => "cesec200" "titulo" => "AUTHOR CONTRIBUTIONS" ] 6 => array:2 [ "identificador" => "xack639212" "titulo" => "ACKNOWLEDGEMENT" ] 7 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-01-06" "fechaAceptado" => "2015-06-01" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "KEYWORDS" "identificador" => "xpalclavsec1582180" "palabras" => array:6 [ 0 => "Elemene" 1 => "Radiosensitivity" 2 => "A549 cells" 3 => "DNA-PKcs" 4 => "Bcl-2" 5 => "p53" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "resumen" => "OBJECTIVE:To investigate the effect of elemene on the radiosensitivity of A549 cells and its possible molecular mechanism. METHODS:Apoptosis of A549 cells was detected by flow cytometry and fluorescence microscopy. The effect of double-strand break (DSB) damage repair in A549 cells was evaluated using the neutral comet assay. Protein expression levels were detected using western blotting, and the correlation between protein levels was analyzed. RESULTS:Elemene exhibited a radiosensitizing effect on A549 cells. The level of apoptosis induced by elemene combined with radiation was significantly greater (p<0.01) than that elicited by either radiation or elemene alone. Following radiation and subsequent repair for 24 h, the tail intensity of A549 cells treated with a combination of elemene and radiation was greater than that of cells treated with either elemene or radiation alone (p<0.01). This result indicates that elemene inhibits cellular DSB repair. Both elemene combined with radiation and radiation alone decreased the protein expression of DNA-PKcs and Bcl-2 compared to elemene alone (p<0.01), while p53 protein expression was increased (p<0.01). A negative correlation was observed between DNA-PKcs and p53 expression (r=-0.569, p=0.040), while a positive correlation was found between DNA-PKcs and Bcl-2 expression (r=0.755, p=0.012). CONCLUSIONS:Elemene exhibits a radiosensitizing effect on A549 cells, and its underlying molecular mechanism of action may be related to the downregulation of DNA-PKcs gene expression." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "ceabs10" "titulo" => "OBJECTIVE:" ] 1 => array:2 [ "identificador" => "ceabs20" "titulo" => "METHODS:" ] 2 => array:2 [ "identificador" => "ceabs30" "titulo" => "RESULTS:" ] 3 => array:2 [ "identificador" => "ceabs40" "titulo" => "CONCLUSIONS:" ] ] ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "No potential conflict of interest was reported." ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 492 "Ancho" => 734 "Tamanyo" => 30784 ] ] "descripcion" => array:1 [ "en" => "Cell survival curves of A549 cells following treatment with 0, 10 or 20 µg/mL elemene and exposure to x-ray doses from 0 to 10 Gy." ] ] 1 => array:7 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1453 "Ancho" => 733 "Tamanyo" => 88280 ] ] "descripcion" => array:1 [ "en" => "Elemene induces apoptosis in A549 cells. Cells were incubated with 10 or 20 μg/mL elemene for 24 h, followed by irradiation with 4 Gy X-rays and washing with PBS. (A) Cells were imaged with an Olympus BX-51 fluorescent microscope using appropriate filter cubes. (B) Chromatin condensation was analyzed by fluorescence microscopy after DNA staining with Hoechst 3334. The results are expressed as the mean ± SD of three independent experiments, n=3, **p<0.01 compared to control, ##p<0.01 compared to radiation alone." ] ] 2 => array:7 [ "identificador" => "fig3" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 442 "Ancho" => 772 "Tamanyo" => 38788 ] ] "descripcion" => array:1 [ "en" => "Influence of elemene on radiation-induced DSB. A549 cells were irradiated with 4 Gy X-rays in the absence or presence of elemene (10 or 20 μg/mL) and assayed immediately after radiation or returned to the incubator for 24 h to permit repair. Comet assays were performed immediately after incubation with elemene treatment, irradiation, or combination treatment. Columns represent the means of the tail moments from three independent experiments, and the bars represent the SD, **p<0.01 vs. control, ##p<0.01 compared to radiation alone." ] ] 3 => array:7 [ "identificador" => "fig4" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 973 "Ancho" => 780 "Tamanyo" => 88632 ] ] "descripcion" => array:1 [ "en" => "Western blot analysis of the protein levels of Bcl-2, p53 and DNA-PKcs. A549 cells were irradiated with 4 Gy X-rays following treatment with 10 or 20 μg/mL elemene for 24 h. Proteins were extracted and separated by SDS-PAGE. (A) Levels of Bcl-2, p53 and DNA-PKcs were quantitated by densitometry, and the ratios of the three proteins are displayed. Values represent the mean ± SD, n=3, **p<0.01 compared to the control, ##p<0.01 compared to radiation alone. Elemene inhibited the protein expression of (B) DNA-PKcs and (C) Bcl-2 and promoted the protein expression of p53. Key: 1, Control; 2, irradiation; 3, 10 μg/mL; 4, 20 μg/mL; 5, 10 μg/mL + irradiation; 6, 20 μg/mL + irradiation." ] ] 4 => array:7 [ "identificador" => "tbl1" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Cells were incubated with 10 or 20 μg/mL concentrations of elemene for 24 h and were then irradiated with 0, 2, 4, 6, 8, and 10 Gy and cultured for another 14 days. The number of cells forming more than 50 clones was counted under the inverted microscope to calculate the cloning efficiency (CE): CE (%)=(Clone formation average of treatment group/inoculated cell number) × 100%. Survival fraction (SF)=(irritated group CE/non-irradiated group PE) × 100%. The experiment was repeated 3 times to calculate the average." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Group \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">0 Gy \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">2 Gy \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">4 Gy \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">6 Gy \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">8 Gy \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">10 Gy \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">84.1±13.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">70.2±10.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">66.3±1.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">47.3±2.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">26.0±1.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">10 μg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">97.7±20.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">76.2±10.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">49.5±6.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">22.5±2.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">7.5±1.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">3.4±0.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">20 μg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">95.4±18.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">63.6±7.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">30.4±3.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">5.7±1.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">2.7±0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">0.7±0.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Survival fraction (%)." ] ] 5 => array:7 [ "identificador" => "tbl2" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "SPSS17.0 was used to calculate survival parameters including SF2 (surviving fraction of 2 Gy), D0 (mean lethal dose or final slope), and Dq (quasi-thres-hold dose). SER (sensitization enhancement ratio). SER D0 (Dq)=control group D0 (Dq)/drug group D0 (Dq). Three parallel samples were set at each radiation dosage." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Group \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">D0 (Gy) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">Dq (Gy) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">SF2 (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">SERD0 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">SERDq \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">2.54±0.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">2.68±0.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">84.6±20.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">- \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">10 μg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.64±0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.87±0.22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">56.3±14.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.54±0.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.43±0.15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">20 μg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.55±0.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.53±0.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">43.2±10.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.63±0.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.75±0.19 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Radiation parameters for a single-hit multi-target model." ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec10" "bibliografiaReferencia" => array:34 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lung cancer. Radiotherapy in lung cancer: Actual methods and future trends" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ A Maciejczyk \n \t\t\t\t\t\t\t\t """ 1 => """ I Skrzypczynska \n \t\t\t\t\t\t\t\t """ 2 => """ M Janiszewska \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.rpor.2014.04.012" "Revista" => array:7 [ "tituloSerie" => "Rep Pract Oncol Radiother" "fecha" => "2014" "volumen" => "19" "numero" => "6" "paginaInicial" => "353" "paginaFinal" => "360" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25337407" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.rpor.2014.04.012" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/j.rpor.2014.04.012" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Enhanced radiation and chemotherapy-mediated cell killing of human cancer cells by small inhibitory RNA silencing of DNA repair factors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ SJ Collis \n \t\t\t\t\t\t\t\t """ 1 => """ MJ Swartz \n \t\t\t\t\t\t\t\t """ 2 => """ WG Nelson \n \t\t\t\t\t\t\t\t """ 3 => """ TL DeWeese \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Cancer Res" "fecha" => "2003" "volumen" => "63" "numero" => "7" "paginaInicial" => "1550" "paginaFinal" => "1554" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12670903" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evidence for the involvement of DNA-dependent protein kinase in the phenomena of low dose hyper-radiosensitivity and increased radioresistance" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ B Marples \n \t\t\t\t\t\t\t\t """ 1 => """ NE Cann \n \t\t\t\t\t\t\t\t """ 2 => """ CR Mitchell \n \t\t\t\t\t\t\t\t """ 3 => """ PJ Johnston \n \t\t\t\t\t\t\t\t """ 4 => """ MC Joiner \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1080/09553000210166606" "Revista" => array:7 [ "tituloSerie" => "Int J Radiat Biol" "fecha" => "2002" "volumen" => "78" "numero" => "12" "paginaInicial" => "1139" "paginaFinal" => "1147" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12556341" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1080/09553000210166606" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1080/09553000210166606" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Selective inactivation of DNA-dependent protein kinase with antisense oligodeoxynucleotides: consequences for the rejoining of radiation-induced DNA double-strand breaks and radiosensitivity of human cancer cell lines" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ A Sak \n \t\t\t\t\t\t\t\t """ 1 => """ M Stuschke \n \t\t\t\t\t\t\t\t """ 2 => """ R Wurm \n \t\t\t\t\t\t\t\t """ 3 => """ G Schroeder \n \t\t\t\t\t\t\t\t """ 4 => """ B Sinn \n \t\t\t\t\t\t\t\t """ 5 => """ G Wolf \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Cancer Res" "fecha" => "2002" "volumen" => "62" "numero" => "22" "paginaInicial" => "6621" "paginaFinal" => "6624" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12438258" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sensing and repairing DNA double-strand breaks" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ SP Jackson \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1093/carcin/23.5.687" "Revista" => array:7 [ "tituloSerie" => "Carcinogenesis" "fecha" => "2002" "volumen" => "23" "numero" => "5" "paginaInicial" => "687" "paginaFinal" => "696" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12016139" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1093/carcin/23.5.687" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1093/carcin/23.5.687" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Apoptosis as a predictor of paclitaxel-induced radiosensitization in human tumor cell lines" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ B Kurdoglu \n \t\t\t\t\t\t\t\t """ 1 => """ N Cheong \n \t\t\t\t\t\t\t\t """ 2 => """ J Guan \n \t\t\t\t\t\t\t\t """ 3 => """ BW Corn \n \t\t\t\t\t\t\t\t """ 4 => """ WJ Curran Jr \n \t\t\t\t\t\t\t\t """ 5 => """ G Iliakis \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "1999" "volumen" => "5" "numero" => "9" "paginaInicial" => "2580" "paginaFinal" => "2587" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10499636" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Apotosis and Radiosensitivity of Cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ LP Wang \n \t\t\t\t\t\t\t\t """ 1 => """ K Liang \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Foreign Medical Science" "fecha" => "2000" "volumen" => "24" "numero" => "2" "paginaInicial" => "75" "paginaFinal" => "78" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The molecular and cellular basis of radiosensitivity: implications for understanding how normal tissues and tumors respond to therapeutic radiation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ EM Rosen \n \t\t\t\t\t\t\t\t """ 1 => """ S Fan \n \t\t\t\t\t\t\t\t """ 2 => """ S Rockwell \n \t\t\t\t\t\t\t\t """ 3 => """ ID Goldberg \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Cancer Invest" "fecha" => "1999" "volumen" => "17" "numero" => "1" "paginaInicial" => "56" "paginaFinal" => "72" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10999050" "web" => "Medline" ] ] ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "http://dx.doi.org/10.3109/07357909909011718" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biological basis of radiation sensitivity. Part 2: Cellular and molecular determinants of radiosensitivity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ EM Rosen \n \t\t\t\t\t\t\t\t """ 1 => """ S Fan \n \t\t\t\t\t\t\t\t """ 2 => """ ID Goldberg \n \t\t\t\t\t\t\t\t """ 3 => """ S Rockwell \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Oncology (Williston Park)" "fecha" => "2000" "volumen" => "14" "numero" => "5" "paginaInicial" => "741" "paginaFinal" => "757" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10853463" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "In vitro study of radiosensitization of β-elemene in A549 cell line from denocarcinoma of lung" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ H Jiang \n \t\t\t\t\t\t\t\t """ 1 => """ S Ma \n \t\t\t\t\t\t\t\t """ 2 => """ J Feng \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chinese-German J of Clin Oncol" "fecha" => "2009" "volumen" => "8" "numero" => "1" "paginaInicial" => "12" "paginaFinal" => "15" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1007/s10330-008-0139-3" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Down regulation of mammalian target of rapamycin decreases HIF-1α and survivin expression in anoxic lung adenocarcinoma A549 cell to elemene and/or irradiation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ K Zou \n \t\t\t\t\t\t\t\t """ 1 => """ E Tong \n \t\t\t\t\t\t\t\t """ 2 => """ Y Xu \n \t\t\t\t\t\t\t\t """ 3 => """ X Deng \n \t\t\t\t\t\t\t\t """ 4 => """ L Zou \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Tumor Biol" "fecha" => "2014" "volumen" => "35" "numero" => "10" "paginaInicial" => "9735" "paginaFinal" => "9741" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1007/s13277-014-2226-0" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The variation of gene expression profile in radiosensitivity to kidney cancer cells induced by elemenen" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ W Cheng \n \t\t\t\t\t\t\t\t """ 1 => """ JP Li \n \t\t\t\t\t\t\t\t """ 2 => """ ZM Wang \n \t\t\t\t\t\t\t\t """ 3 => """ W Song \n \t\t\t\t\t\t\t\t """ 4 => """ C Huang \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chin J Urol" "fecha" => "2007" "volumen" => "28" "numero" => "2" "paginaInicial" => "87" "paginaFinal" => "90" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A Study of Radiosensitivity of β-Elemene to Squamous Cell Carcinoma of Tongue Tca-8113 Cell Line in Vitro" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ DP Wu \n \t\t\t\t\t\t\t\t """ 1 => """ XM Li \n \t\t\t\t\t\t\t\t """ 2 => """ JF Zhao \n \t\t\t\t\t\t\t\t """ 3 => """ HB Wang \n \t\t\t\t\t\t\t\t """ 4 => """ DQ Zhao \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Journal of Basic and Clinical Oncology" "fecha" => "2006" "volumen" => "19" "numero" => "2" "paginaInicial" => "116" "paginaFinal" => "117" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The study of the β-elemene effect on the augment of radiation treatment in mouse inoculated U14 strain" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ LJ Zou \n \t\t\t\t\t\t\t\t """ 1 => """ XH Sun \n \t\t\t\t\t\t\t\t """ 2 => """ XY Xu \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chin J Radiological Medicine and Protection" "fecha" => "2004" "volumen" => "24" "numero" => "3" "paginaInicial" => "254" "paginaFinal" => "255" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Radiosensitization of beta-elemene on VX2 carcinoma transplanted on kidney in rabbits in vivo" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ JJ She \n \t\t\t\t\t\t\t\t """ 1 => """ ZM Wang \n \t\t\t\t\t\t\t\t """ 2 => """ XM Che \n \t\t\t\t\t\t\t\t """ 3 => """ CE Pan \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.3736/jcim20060415" "Revista" => array:7 [ "tituloSerie" => "Zhong Xi Yi Jie He Xue Bao" "fecha" => "2006" "volumen" => "4" "numero" => "4" "paginaInicial" => "392" "paginaFinal" => "396" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16834978" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.3736/jcim20060415" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.3736/jcim20060415" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib16" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "β-Elemene radiosensitizes lung cancer A549 cells by enhancing DNA damage and inhibiting DNA repair" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ LJ Li \n \t\t\t\t\t\t\t\t """ 1 => """ LF Zhong \n \t\t\t\t\t\t\t\t """ 2 => """ LP Jiang \n \t\t\t\t\t\t\t\t """ 3 => """ CY Geng \n \t\t\t\t\t\t\t\t """ 4 => """ LJ Zou \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1002/ptr.3367" "Revista" => array:7 [ "tituloSerie" => "Phytother Res" "fecha" => "2011" "volumen" => "25" "numero" => "7" "paginaInicial" => "1095" "paginaFinal" => "1097" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22692988" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1002/ptr.3367" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1002/ptr.v25.7" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib17" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Survival and tumour control probability in tumours withheterogeneous oxygenation: A comparison between the linearquadratic and the universal survival curve models for high doses" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ E Lindblom \n \t\t\t\t\t\t\t\t """ 1 => """ A Dasu \n \t\t\t\t\t\t\t\t """ 2 => """ I Lax \n \t\t\t\t\t\t\t\t """ 3 => """ I Toma-Dasu \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.3109/0284186X.2014.925582" "Revista" => array:7 [ "tituloSerie" => "Acta Oncol" "fecha" => "2014" "volumen" => "53" "numero" => "8" "paginaInicial" => "1035" "paginaFinal" => "1040" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24957551" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.3109/0284186X.2014.925582" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.3109/0284186X.2014.925582" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib18" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Variation in the measurement of DNA damage by comet assay measured by the ECVAG inter-laboratory validation trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ L Forchhammer \n \t\t\t\t\t\t\t\t """ 1 => """ C Johansson \n \t\t\t\t\t\t\t\t """ 2 => """ S Loft \n \t\t\t\t\t\t\t\t """ 3 => """ L Moller \n \t\t\t\t\t\t\t\t """ 4 => """ RW Godschalk \n \t\t\t\t\t\t\t\t """ 5 => """ SA Langie \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1093/mutage/gep048" "Revista" => array:7 [ "tituloSerie" => "Mutagenesis" "fecha" => "2010" "volumen" => "25" "numero" => "2" "paginaInicial" => "113" "paginaFinal" => "123" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19910383" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1093/mutage/gep048" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1093/mutage/gep048" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib19" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The lysosomal-mitochondrial axis in free fatty acid-induced hepatic lipotoxicity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ Z Li \n \t\t\t\t\t\t\t\t """ 1 => """ M Berk \n \t\t\t\t\t\t\t\t """ 2 => """ TM McIntyre \n \t\t\t\t\t\t\t\t """ 3 => """ GJ Gores \n \t\t\t\t\t\t\t\t """ 4 => """ AE Feldstein \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1002/hep.22183" "Revista" => array:7 [ "tituloSerie" => "Hepatology" "fecha" => "2008" "volumen" => "47" "numero" => "5" "paginaInicial" => "1495" "paginaFinal" => "1503" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18220271" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1002/hep.22183" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1002/(ISSN)1527-3350" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib20" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Down-regulation of survivin and hypoxia-inducible factor-1 alpha by beta-elemene enhances the radiosensitivity of lung adenocarcinoma xenograft" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ G Li \n \t\t\t\t\t\t\t\t """ 1 => """ B Xie \n \t\t\t\t\t\t\t\t """ 2 => """ X Li \n \t\t\t\t\t\t\t\t """ 3 => """ Y Chen \n \t\t\t\t\t\t\t\t """ 4 => """ Q Wang \n \t\t\t\t\t\t\t\t """ 5 => """ Y Xu \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1089/cbr.2011.1003" "Revista" => array:7 [ "tituloSerie" => "Cancer Biother Radiopharm" "fecha" => "2012" "volumen" => "27" "numero" => "1" "paginaInicial" => "56" "paginaFinal" => "64" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22248028" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1089/cbr.2011.1003" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1089/cbr.2011.1003" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib21" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Enhancement of gastric cancer MKN28 cell line radiosensitivity induced by beta-elemene" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ S He \n \t\t\t\t\t\t\t\t """ 1 => """ J Liu \n \t\t\t\t\t\t\t\t """ 2 => """ Z Zhang \n \t\t\t\t\t\t\t\t """ 3 => """ X Che \n \t\t\t\t\t\t\t\t """ 4 => """ L Fan \n \t\t\t\t\t\t\t\t """ 5 => """ S Chang \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Zhonghua Wai Ke Za Zhi" "fecha" => "2014" "volumen" => "52" "numero" => "6" "paginaInicial" => "442" "paginaFinal" => "445" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25219560" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib22" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "β-Elemene against human lung cancer via up-regulation of P53 protein expression to promote the release of exosome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ J Li \n \t\t\t\t\t\t\t\t """ 1 => """ A JunYu, Liu \n \t\t\t\t\t\t\t\t """ 2 => """ Y Wang \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.lungcan.2014.08.015" "Revista" => array:7 [ "tituloSerie" => "Lung Cancer" "fecha" => "2014" "volumen" => "86" "numero" => "2" "paginaInicial" => "144" "paginaFinal" => "150" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25204604" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.lungcan.2014.08.015" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/j.lungcan.2014.08.015" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib23" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effects of β-elemene on the activation of Akt and the expressions of apoptosis-related proteins in gastric cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ Y Zhang \n \t\t\t\t\t\t\t\t """ 1 => """ MF Zhao \n \t\t\t\t\t\t\t\t """ 2 => """ YP Liu \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Shanxi Oncology Medicine" "fecha" => "2012" "volumen" => "3" "paginaInicial" => "451" "paginaFinal" => "454" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib24" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Influence on apoptosis relevant protein expression of human lung adenocarcinoma A549 cell line managed by Elemene" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ XQ Zhou \n \t\t\t\t\t\t\t\t """ 1 => """ XJ Qiu \n \t\t\t\t\t\t\t\t """ 2 => """ HY Zhao \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Journal of Modern Oncology" "fecha" => "2012" "volumen" => "20" "numero" => "10" "paginaInicial" => "2027" "paginaFinal" => "2030" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib25" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Study on inhibition of the expression of c-myc gene of human glioma U251cell line and the effect mechanism of effect on cellular apoptosis by elemene" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ WZ Yang \n \t\t\t\t\t\t\t\t """ 1 => """ CM Chen \n \t\t\t\t\t\t\t\t """ 2 => """ SS Shi \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chin J Clin Oncol" "fecha" => "2005" "volumen" => "32" "numero" => "13" "paginaInicial" => "763" "paginaFinal" => "766" ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib26" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of β-elemene combined with radiotherapy on the expression of Livin mRNA and apoptosis of lung adenocarcinoma cell line A549" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ QT Zhao \n \t\t\t\t\t\t\t\t """ 1 => """ Y Yang \n \t\t\t\t\t\t\t\t """ 2 => """ CB Sun \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Journal of Modern Oncology" "fecha" => "2013" "volumen" => "21" "numero" => "2" "paginaInicial" => "257" "paginaFinal" => "260" ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib27" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ P Calsou \n \t\t\t\t\t\t\t\t """ 1 => """ C Delteil \n \t\t\t\t\t\t\t\t """ 2 => """ P Frit \n \t\t\t\t\t\t\t\t """ 3 => """ J Drouet \n \t\t\t\t\t\t\t\t """ 4 => """ B Salles \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/s0022-2836(02)01328-1" "Revista" => array:7 [ "tituloSerie" => "J Mol Biol" "fecha" => "2003" "volumen" => "326" "numero" => "1" "paginaInicial" => "93" "paginaFinal" => "103" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12547193" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/s0022-2836(02)01328-1" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/S0022-2836(02)01328-1" ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib28" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Correlation of DNA-dependent protein kinase catalytic subunit expression to radiosensitivity of non-small cell lung cancer cell lines" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ Y Pan \n \t\t\t\t\t\t\t\t """ 1 => """ WX Li \n \t\t\t\t\t\t\t\t """ 2 => """ JM Li \n \t\t\t\t\t\t\t\t """ 3 => """ JQ Zhu \n \t\t\t\t\t\t\t\t """ 4 => """ YQ Liang \n \t\t\t\t\t\t\t\t """ 5 => """ AL Guo \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5732/cjc.009.10013" "Revista" => array:7 [ "tituloSerie" => "Ai Zheng" "fecha" => "2009" "volumen" => "28" "numero" => "7" "paginaInicial" => "714" "paginaFinal" => "717" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19624897" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib29" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "DNA-PKcs silencing inhibit the DNA repair induced by low dose radiation on human breast epithelial cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ W Zou \n \t\t\t\t\t\t\t\t """ 1 => """ J Che \n \t\t\t\t\t\t\t\t """ 2 => """ CJ Wang \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chin J Biotech" "fecha" => "2009" "volumen" => "25" "numero" => "5" "paginaInicial" => "727" "paginaFinal" => "732" ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib30" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhibition of DNA-PKcs by siRNA and its effect on the growth of HeLa cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ J An \n \t\t\t\t\t\t\t\t """ 1 => """ JL Sui \n \t\t\t\t\t\t\t\t """ 2 => """ QZ Xu \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4269/ajtmh.21-1184" "Revista" => array:7 [ "tituloSerie" => "Carcinogenesis, Teratogenesis & Mutagenesis" "fecha" => "2005" "volumen" => "17" "numero" => "6" "paginaInicial" => "327" "paginaFinal" => "331" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35895428" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib31" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mechanism of non-homologous end joing and its bilolgical implications" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ YQ Yan \n \t\t\t\t\t\t\t\t """ 1 => """ PK Zhou \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Journal of Medical Molecular Biology" "fecha" => "2006" "volumen" => "3" "numero" => "1" "paginaInicial" => "69" "paginaFinal" => "72" ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib32" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The expression of DNA-PKcs in non-small cell lung cancer and its relationship with apoptosis associated proteins" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ S Yu \n \t\t\t\t\t\t\t\t """ 1 => """ Y Xiong \n \t\t\t\t\t\t\t\t """ 2 => """ S Tian \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3779/j.issn.1009-3419.2003.05.08" "Revista" => array:7 [ "tituloSerie" => "Zhongguo Fei Ai Za Zhi" "fecha" => "2003" "volumen" => "6" "numero" => "5" "paginaInicial" => "356" "paginaFinal" => "359" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21306678" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib33" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhibition of the DNA-dependent protein kinase catalytic subunit radiosensitizes malignant glioma cells by inducing autophagy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ S Daido \n \t\t\t\t\t\t\t\t """ 1 => """ A Yamamoto \n \t\t\t\t\t\t\t\t """ 2 => """ K Fujiwara \n \t\t\t\t\t\t\t\t """ 3 => """ R Sawaya \n \t\t\t\t\t\t\t\t """ 4 => """ S Kondo \n \t\t\t\t\t\t\t\t """ 5 => """ Y Kondo \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1158/0008-5472.CAN-04-4202" "Revista" => array:7 [ "tituloSerie" => "Cancer Res" "fecha" => "2005" "volumen" => "65" "numero" => "10" "paginaInicial" => "4368" "paginaFinal" => "4375" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15899829" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1158/0008-5472.CAN-04-4202" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1158/0008-5472.CAN-04-4202" ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib34" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The p53-inducible gene 3 (PIG3) contributes to early cellular response to DNA damage" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ JH Lee \n \t\t\t\t\t\t\t\t """ 1 => """ Y Kang \n \t\t\t\t\t\t\t\t """ 2 => """ V Khare \n \t\t\t\t\t\t\t\t """ 3 => """ ZY Jin \n \t\t\t\t\t\t\t\t """ 4 => """ MY Kang \n \t\t\t\t\t\t\t\t """ 5 => """ Y Yoon \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1038/onc.2009.438" "Revista" => array:7 [ "tituloSerie" => "Oncogene" "fecha" => "2010" "volumen" => "29" "numero" => "10" "paginaInicial" => "1431" "paginaFinal" => "1450" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20023697" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1038/onc.2009.438" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1038/onc.2009.438" ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack639212" "titulo" => "ACKNOWLEDGEMENT" "texto" => "This study was supported by grants from the National Natural Science Foundation of China (No. 81473452)." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/18075932/0000007000000008/v1_202212011321/S1807593222013473/v1_202212011321/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/18075932/0000007000000008/v1_202212011321/S1807593222013473/v1_202212011321/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222013473?idApp=UINPBA00004N"]

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Kun Zou, Caigang Liu, Zhuo Zhang

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799832582@qq.com

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, Lijuan Zou

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zoulijuanfl@163.com

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2nd Affiliated Hospital of Dalian Medical University, Radiotherapy Department, Dalian/Liaoning, China

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          "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Western blot analysis of the protein levels of Bcl-2&#44; p53 and DNA-PKcs&#46; A549 cells were irradiated with 4 Gy X-rays following treatment with 10 or 20 &#956;g&#47;mL elemene for 24 h&#46; Proteins were extracted and separated by SDS-PAGE&#46; <span class="elsevierStyleBold">&#40;A&#41;</span> Levels of Bcl-2&#44; p53 and DNA-PKcs were quantitated by densitometry&#44; and the ratios of the three proteins are displayed&#46; Values represent the mean &#177; SD&#44; n&#61;3&#44; <span class="elsevierStyleSup">&#42;&#42;</span><span class="elsevierStyleItalic">p&#60;</span>0&#46;01 compared to the control&#44; <span class="elsevierStyleSup">&#35;&#35;</span><span class="elsevierStyleItalic">p&#60;</span>0&#46;01 compared to radiation alone&#46; Elemene inhibited the protein expression of <span class="elsevierStyleBold">&#40;B&#41;</span> DNA-PKcs and <span class="elsevierStyleBold">&#40;C&#41;</span> Bcl-2 and promoted the protein expression of p53&#46; Key&#58; 1&#44; Control&#59; 2&#44; irradiation&#59; 3&#44; 10 &#956;g&#47;mL&#59; 4&#44; 20 &#956;g&#47;mL&#59; 5&#44; 10 &#956;g&#47;mL &#43; irradiation&#59; 6&#44; 20 &#956;g&#47;mL &#43; irradiation&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Lung cancer is one of the most common malignant tumors&#44; and radiotherapy is the prevailing method of choice for treatment <a class="elsevierStyleCrossRef" href="#bib1">1</a>&#44; especially for middle- to late-stage lung cancer&#46; Radiation works by damaging the DNA of cancerous cells and altering apoptosis-related genes or proteins&#44; leading to cell death&#46; Improving the radiosensitivity of tumor cells is a significant factor that would improve the efficacy of radiotherapy&#46;</p><p id="para20" class="elsevierStylePara elsevierViewall">DNA-dependent protein kinase &#40;DNA-PK&#41; is an important enzyme that participates in DNA damage repair and has become the main target of radiation sensitivity interventions <a class="elsevierStyleCrossRef" href="#bib2">2</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib4">4</a>&#46; The catalytic subunit &#40;cs&#41; of DNA-PK affects cellular radiosensitivity by regulating the phosphorylation of DNA damage repair-related proteins <a class="elsevierStyleCrossRef" href="#bib5">5</a>&#46; Thus&#44; inhibition of DNA-PKcs gene expression can block DNA double-strand break &#40;DSB&#41; repair and improve cellular radiosensitivity&#46;</p><p id="para30" class="elsevierStylePara elsevierViewall">Cellular apoptosis is the core characteristic of radiotherapy&#44; and regulation of this process thus plays an important role in cellular radiosensitivity <a class="elsevierStyleCrossRef" href="#bib6">6</a>&#44;<a class="elsevierStyleCrossRef" href="#bib7">7</a>&#46; Previous studies have shown that apoptosis-related genes&#44; such as phosphoprotein &#40;p53&#41;&#44; p16&#44; B-cell lymphoma-2 &#40;Bcl-2&#41;&#44; and erythroblastic leukemia viral oncogene homolog 2 &#40;erbB-2&#41;&#44; are associated with tumor radiosensitivity <a class="elsevierStyleCrossRef" href="#bib8">8</a>&#44;<a class="elsevierStyleCrossRef" href="#bib9">9</a>&#44; especially p53 and Bcl-2&#46; It has also been reported that elemene interacts with the frontier orbitals of DNA bases to form complexes between DNA molecules&#46; Specifically&#44; Jiang et al&#46; <a class="elsevierStyleCrossRef" href="#bib10">10</a> showed that elemene increases the radiosensitivity of A549 cells&#44; the mechanism for which may be related to the upregulation of p53&#44; downregulation of Bcl-2&#44; and induction of cellular apoptosis&#46;</p><p id="para40" class="elsevierStylePara elsevierViewall">Elemene&#44; which is extracted from Zingiberaceae plants &#40;<span class="elsevierStyleItalic">Curcuma aromatica</span> Salisb&#46;&#41;&#44; is a non-cytotoxic antitumor compound that can improve the radiosensitivity of tumor cells <a class="elsevierStyleCrossRef" href="#bib11">11</a>&#46; Results of an <span class="elsevierStyleItalic">in vitro</span> study showed that elemene increased the radiosensitivity of renal carcinoma cells&#44; tongue squamous cancer cells&#44; and non-small cell lung cancer cells <a class="elsevierStyleCrossRef" href="#bib10">10</a>&#44;<a class="elsevierStyleCrossRef" href="#bib12">12</a>&#44;<a class="elsevierStyleCrossRef" href="#bib13">13</a>&#46; Animal experiments further showed that elemene exhibited radiotherapy-sensitizing effects in many types of tumor cells&#44; such as transplanted murine U14 tumors&#44; kidney cancer GRC-1 cells&#44; and tongue squamous carcinoma Tca-8113 cells <a class="elsevierStyleCrossRef" href="#bib13">13</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib15">15</a>&#46; In addition&#44; beta elemene enhances A549 cell radiosensitivity through enhancement of DNA damage and suppression of DNA repair <a class="elsevierStyleCrossRef" href="#bib16">16</a>&#46;</p><p id="para50" class="elsevierStylePara elsevierViewall">In the current study&#44; A549 cells were irradiated following elemene treatment&#44; and the changes in expression of the apoptosis-related genes Bcl-2 and p53 as well as the double-stranded DNA damage repair-related gene DNA-PKcs were evaluated&#46; These experiments were conducted to further understand elemene&#39;s molecular mechanism of action in enhancing radiation sensitivity of A549 cells&#46;</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">MATERIALS AND METHODS</span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">Cell culture</span><p id="para60" class="elsevierStylePara elsevierViewall">The human lung adenocarcinoma A549 cell line was purchased from the Chinese Academy of Medical Sciences &#40;CAMS&#41; Cell Center and passaged at the Second Affiliated Hospital of Dalian Medical University Center Laboratory&#46; The cells were cultured in RPMI 1640 medium containing 10&#37; inactivated fetal bovine serum &#40;FBS&#41; at 37&#176;C under an atmosphere of 5&#37; CO<span class="elsevierStyleInf">2</span> and saturated humidity&#46; The cells were subcultured when they reached the exponential phase&#46;</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">Reagents and instruments</span><p id="para70" class="elsevierStylePara elsevierViewall">Elemene &#40;0&#46;1 g&#47;20 mL&#41;&#44; which was obtained from DaLian JinGang Pharmaceutical Co&#46; Ltd&#46; &#40;China&#41;&#44; was dissolved in RPMI 1640 medium to final working concentrations of 10 and 20 &#181;g&#47;mL before use&#46; RPMI 1640 medium was obtained from Gibco &#40;USA&#41;&#59; FBS was obtained from TianJin TBD Biotechnology Company &#40;China&#41;&#59; p53 and Bcl-2 antibodies were obtained from Santa Cruz &#40;USA&#44; 1&#58;1&#44;000&#41;&#59; and DNA-PKcs antibody &#40;1&#58;2&#44;000&#41;&#44; anti-human &#946;-actin mouse monoclonal antibody and histone H1 internuclear internal reference antibodies &#40;1&#58;200&#41; were obtained from Neomarker &#40;USA&#41;&#46; The Jim-X half-dry transfer electrophoresis apparatus was obtained from DaLian JingMai Biotechnology Co&#46; Ltd&#46; &#40;China&#41;&#46; The flow cytometer was purchased from the Gene Company &#40;USA&#41;&#46; The CK2 type inverted microscope was obtained from Olympus &#40;Japan&#41;&#46; The BX51 type fluorescent microscope was also obtained from Olympus &#40;Japan&#41;&#46;</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">Irradiation conditions</span><p id="para80" class="elsevierStylePara elsevierViewall">Cell irradiation was performed using the Varian 2300C&#47;D medical linear accelerator &#40;Varian Companies&#44; USA&#41; with a coverage field of 20 cm &#215; 20 cm&#46; The culture dish was placed in the radiation field above 1&#46;5 cm of organic glass&#46; Cells with irradiated with 6 MV X-ray irradiation at a dosage rate of 300 cGy&#47;min&#44; a rack angle of 180&#176;&#44; and source-to-surface distance &#40;SSD&#41; of 100 cm&#46;</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">Clonogenic assay</span><p id="para90" class="elsevierStylePara elsevierViewall">Logarithmic-growth phase cells were inoculated in a 60-mm culture dish&#46; After adherence&#44; the cells in the drug and combined irradiation groups were cultured in the presence of 10 or 20 &#956;g&#47;mL elemene and seeded in culture plates at 100 cells&#47;well for 24 h&#46; The cells were exposed to 0&#44; 2&#44; 4&#44; 6&#44; 8&#44; and 10 Gy of irradiation and cultured for another 14 days&#46; The number of cell clones viewed under a low magnification microscope was 50&#46; The plating efficiency &#40;PE&#41; was calculated relative to the control group &#40;0 Gy&#41;&#44; and the survival fraction &#40;SF&#41; of each group was calculated as follows&#58; SER&#61;control group &#40;<span class="elsevierStyleInf">D0&#44; Dq</span>&#41;&#47;experimental group &#40;D0&#44; Dq&#41;&#46;</p></span><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle120">Morphological assessment of apoptosis</span><p id="para100" class="elsevierStylePara elsevierViewall">The cells were treated as follows&#58; the control group received RPMI 1640 medium&#59; the radiation group received a radiation dose of 4 Gy&#59; the drug group was treated with 10 or 20 &#181;g&#47;mL elemene&#59; and the drug plus radiation group was treated with 10 or 20 &#181;g&#47;mL elemene followed by a radiation dose of 4 Gy&#46; Following incubation with elemene&#44; the exponentially growing cells were irradiated as described above&#46; Samples of 3 &#215; 10<span class="elsevierStyleSup">5</span> cells were then collected from each group&#44; treated with pancreatic enzyme digesting cells&#44; rinsed twice with PBS&#44; and centrifuged at 1&#44;000 rpm for 5 min&#46; The SF was determined using the following equation&#58; SF&#61;colony number&#47;&#40;plating cell number &#215; PE&#41;&#46;</p><p id="para110" class="elsevierStylePara elsevierViewall">The dose survival curve was fitted using the linear-quadratic &#40;LQ&#41; function model <span class="elsevierStyleItalic">S</span>&#61;e-&#40;&#945;d&#43;&#946;d2&#41; <a class="elsevierStyleCrossRef" href="#bib17">17</a> for calculating radiobiological parameters&#44; including the sensitivity enhancement ratio &#40;SER&#41;&#44; SER of the mean lethal dose &#40;D0&#41; SER<span class="elsevierStyleInf">Dq&#44;</span> and SER of the quasi-threshold dose &#40;Dq&#41; SER<span class="elsevierStyleInf">D0</span>&#46; Nuclear morphology was examined using fluorescence microscopy following Hoechst 33342 staining &#40;final concentration 8 mg&#47;mL&#41; for 15 min at 37&#176;C&#46; Imaging was performed using an Olympus BX-51 fluorescent microscope with appropriate filter cubes&#46; The excitation and emission wavelengths were 350 nm 460 nm&#44; respectively&#46;</p></span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle130">Apoptosis standard</span><p id="para120" class="elsevierStylePara elsevierViewall">Normal cells demonstrated uniform dispersion of low-density fluorescence&#44; while apoptotic cells showed high-density fluorescence&#44; characterized by a bright blue hue&#46;</p></span><span id="cesec90" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle140">Assessment of apoptosis</span><p id="para130" class="elsevierStylePara elsevierViewall">The cells used were grouped and treated as specified above&#46; Then&#44; samples of 3 &#215; 10<span class="elsevierStyleSup">5</span> cells were collected from each group&#44; treated with pancreatic enzyme digesting cells&#44; rinsed twice with PBS&#44; and centrifuged at 1&#44;000 rpm for 5 min&#46; The cells were treated with 100 &#956;L 2&#37; Triton X-100 for 20 min&#44; rinsed twice with PBS&#44; and centrifuged at 1&#44;000 rpm for 5 min&#46; Next&#44; 200 &#956;L of DNA-Prep LPR reagent &#40;Beckman-Coulter Ltd&#41; was added for 20 min&#44; and the cells were rinsed twice with PBS&#44; followed by centrifugation at 1&#44;000 rpm for 5 min&#46; The cells were resuspended in PBS and 50 &#181;g&#47;mL propidium iodide &#40;PI&#41; reagent containing 480 &#956;L of PBS&#44; 5 &#956;L of PI &#40;5 mg &#47;mL&#41;&#44; and 5 &#956;L of RNase &#40;10 mg &#47;mL&#41;&#44; and 10 &#956;L of Triton X-100 &#40;10&#37;&#41; was added 30 s later&#46; Single-cell suspensions were analyzed by flow cytometry to determine the cellular apoptosis rate&#46;</p></span><span id="cesec100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle150">Neutral comet assay</span><p id="para140" class="elsevierStylePara elsevierViewall">A549 cells were irradiated in the absence or presence of elemene &#40;10 or 20 &#181;g&#47;mL&#41; and assayed immediately after radiation or returned to the incubator for 24 h to permit repair&#46; The comet assays were performed immediately after incubation with elemene&#44; irradiation or combination treatment&#46; Tumor cells were grown on glass microscope slides using a standard protocol <a class="elsevierStyleCrossRef" href="#bib18">18</a>&#46; The slides were submerged in lysing solution containing 30 mM ethylenediaminetetraacetic acid &#40;EDTA&#41; and 0&#46;5&#37; sodium dodecyl sulfate &#40;SDS&#44; pH 8&#46;3&#41; for 1&#46;5 h at 37&#176;C&#46; Following lysis&#44; the slides were rinsed three times in Tris-borate-EDTA &#40;TBE&#41; buffer consisting of 90 mM Tris&#44; 90 mM boric acid&#44; and 2 mM EDTA&#44; pH 8&#46;5&#44; and stored overnight in TBE buffer at 4&#176;C&#46; Slides were transferred to an electrophoresis unit with TBE buffer and electrophoresed at 1 V&#47;cm for 20 min&#46; Following electrophoresis&#44; the slides were neutralized with 0&#46;4 M Tris buffer &#40;pH 7&#46;5&#41; and stained with ethidium bromide &#40;20 &#181;g&#47;mL&#41;&#46; Finally&#44; the slides were viewed using an Olympus BX&#8208;51 fluorescent microscope &#40;excitation filter 549 nm&#44; barrier filter 590 nm&#41;&#46; Images of 50 randomly selected cells from each slide were analyzed with Comet Assay Software Project casp&#8208;1&#46;2&#46;2 &#40;University of Wroclaw&#44; Poland&#41;&#46; The tail moment was used as a parameter to assess DNA damage&#46; The assay was completed three separate times&#44; and 50 cells were evaluated per experiment&#46;</p></span><span id="cesec110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle160">Western blot assay</span><p id="para150" class="elsevierStylePara elsevierViewall">Western blotting was performed to detect the expression levels of DNA-PKcs&#44; p53&#44; and Bcl-2&#46; The cells were grouped and treated as specified above&#46; After 24 h&#44; western blot analysis was performed using cytosolic fractions as previously described <a class="elsevierStyleCrossRef" href="#bib19">19</a>&#46; Equal amounts of cytosolic protein were separated on 8&#8211;12&#37; SDS polyacrylamide denaturing gels and transferred to nitrocellulose membranes&#46; The membranes were blocked in TBS-Tween &#40;TBS-T&#44; 10 mM Tris-HCl&#44; pH 7&#46;4&#59; 150 mM NaCl&#59; and 0&#46;1&#37; Tween-20&#41; with 5&#37; non-fat milk for 2 h and incubated with specific primary antibodies overnight at 4&#176;C&#46; Finally&#44; the membranes were incubated with horseradish peroxidase &#40;HRP&#41;-conjugated secondary antibodies at 37&#176;C for 2 h and assayed using an enhanced chemiluminescence plus detection system&#46;</p></span><span id="cesec120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle170">Statistical analysis</span><p id="para160" class="elsevierStylePara elsevierViewall">Data were analyzed using the statistical package for the social sciences &#40;SPSS&#41; v13&#46;0 software&#46; Data are expressed as the mean &#177; standard deviation &#40;SD&#41;&#46; The statistical significance of differences between groups was determined by one-way analysis of variance &#40;ANOVA&#41;&#44; followed by post hoc analysis using the least significant difference &#40;LSD&#41; for multiple comparisons&#46; The Spearman test was used for the correlation analysis of the relationships between the expression levels of genes&#46; The level of significance was set at <span class="elsevierStyleItalic">p&#60;</span>0&#46;05 and <span class="elsevierStyleItalic">p</span>&#60;0&#46;01 for all statistical analysis&#46;</p></span></span><span id="cesec130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle180">RESULTS</span><span id="cesec140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle190">Effects of elemene on cell radiosensitivity</span><p id="para170" class="elsevierStylePara elsevierViewall">The survival fraction of A549 cells decreased following treatment with different doses of radiation and the same concentration of elemene&#46; Conversely&#44; the A549 cell survival fraction decreased in the groups treated with the same dose of radiation in combination with increasing concentrations of elemene &#40;<a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>&#41;&#46; Following treatment with 10 or 20 &#956;g&#47;mL elemene&#44; the A549 cell survival curve shifted to the left&#44; the shoulder area was diminished&#44; and the steepness of the curve increased &#40;<a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>&#41;&#46; Based on the cell survival curve&#44; the radiobiological parameters and radiosensitization ratio were obtained and are listed in <a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>&#46; These data show that&#44; compared with the control group&#44; the SER<span class="elsevierStyleInf">D0</span> and SER<span class="elsevierStyleInf">Dq</span> values for the 10 and 20 &#956;g&#47;mL elemene treatment groups were greater than 1&#46; Furthermore&#44; the ratio gradually increased with an increasing drug concentration &#40;<a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia><elsevierMultimedia ident="fig1"></elsevierMultimedia><elsevierMultimedia ident="tbl2"></elsevierMultimedia></span><span id="cesec150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle200">Effect of elemene on A549 cell apoptosis</span><p id="para180" class="elsevierStylePara elsevierViewall">Fluorescence microscopy showed that compared with the control group&#44; the groups treated with radiation alone and elemene alone contained more apoptotic cells &#40;<a class="elsevierStyleCrossRef" href="#fig2">Figure 2</a>&#41;&#46; Furthermore&#44; significantly higher apoptotic levels were observed in the groups treated with radiation and elemene at 10 or 20 &#956;g&#47;mL &#40;<a class="elsevierStyleCrossRef" href="#fig2">Figure 2A</a>&#41;&#46; Flow cytometry revealed that compared with the control group&#44; the apoptosis rate of the group treated with radiation alone appeared to increase&#44; but this was not found to be statistically significant &#40;<span class="elsevierStyleItalic">p</span>&#62;0&#46;05&#41;&#46; The apoptosis rate of the group treated with elemene alone did not change &#40;<span class="elsevierStyleItalic">p</span>&#62;0&#46;05&#41;&#44; while the apoptosis rate of the elemene plus radiation group increased significantly &#40;<span class="elsevierStyleItalic">p&#60;</span>0&#46;01&#41;&#46; The rate of apoptosis increased with increasing concentrations of elemene &#40;<a class="elsevierStyleCrossRef" href="#fig2">Figure 2B</a>&#41;&#46;</p><elsevierMultimedia ident="fig2"></elsevierMultimedia></span><span id="cesec160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle210">Effect of elemene on DSB repair in A549 cells</span><p id="para190" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig3">Figure 3</a> &#40;0 h&#41; shows that both elemene and irradiation alone increased the tail intensity in A549 cells&#44; and the degree of DSB was augmented as the elemene concentration increased&#46; In particular&#44; the results showed a higher number of DSB in the combination group than the irradiation alone and elemene alone groups &#40;<span class="elsevierStyleItalic">p</span>&#60;0&#46;01&#41;&#46; As shown in <a class="elsevierStyleCrossRef" href="#fig3">Figure 3</a> &#40;24 h&#41;&#44; following incubation for 24 h&#44; the tail intensity in the irradiation alone group returned to background levels&#44; while there was a significant increase in the amount of remaining tail intensity in the combination group compared with the irradiation alone and elemene alone groups &#40;<span class="elsevierStyleItalic">p</span>&#60;0&#46;01&#41;&#46;</p><elsevierMultimedia ident="fig3"></elsevierMultimedia></span><span id="cesec170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle220">Effects of elemene on DNA-PKcs&#44; Bcl-2&#44; and p53 protein expression in A549 cells</span><p id="para200" class="elsevierStylePara elsevierViewall">The results shown in <a class="elsevierStyleCrossRef" href="#fig4">Figure 4A</a> revealed that in the 10 and 20 &#956;g&#47;mL combined treatment groups&#44; a significant decrease in the protein expression of DNA-PKcs &#40;<span class="elsevierStyleItalic">p&#60;</span>0&#46;01&#44; <a class="elsevierStyleCrossRef" href="#fig4">Figure 4B</a>&#41; and Bcl-2 &#40;<span class="elsevierStyleItalic">p</span>&#60;0&#46;01&#44; <a class="elsevierStyleCrossRef" href="#fig4">Figure 4C</a>&#41; was observed&#44; while the p53 protein expression level was significantly increased &#40;<span class="elsevierStyleItalic">p&#60;</span>0&#46;01&#44; <a class="elsevierStyleCrossRef" href="#fig4">Figure 4C</a>&#41;&#46;</p><elsevierMultimedia ident="fig4"></elsevierMultimedia></span><span id="cesec180" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle230">Protein expression correlation analysis</span><p id="para210" class="elsevierStylePara elsevierViewall">Spearman correlation analysis showed that DNA-PKcs and p53 protein expression was negatively correlated &#40;r&#61;-0&#46;569&#44; <span class="elsevierStyleItalic">p</span>&#60;0&#46;05&#41;&#44; while DNA-PKcs expression was positively correlated with Bcl-2 protein expression &#40;r&#61;0&#46;755&#44; <span class="elsevierStyleItalic">p&#60;</span>0&#46;05&#41;&#46;</p></span></span><span id="cesec190" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle240">DISCUSSION</span><p id="para220" class="elsevierStylePara elsevierViewall">Basic research in radiation biology has shown that radiation therapy works mainly by damaging tumor cell DNA and altering the expression of apoptosis-related genes and proteins&#46; The radiosensitivity of tumor cells relates to their capacity to repair DSB via the related genes DNA-PKcs&#44; Ku70&#47;80&#44; and ataxia telangiectasia mutated &#40;ATM&#41;&#46; Other genes known to be involved in radiosensitivity and responsible for apoptosis regulation include p53&#44; Bcl-2&#44; c-myc proto-oncogene &#40;c-myc&#41;&#44; and survivin <a class="elsevierStyleCrossRef" href="#bib9">9</a>&#46; Beta elemene&#44; which is the active component of elemene&#44; has recently been demonstrated to enhance the radiosensitivity of human cancer cell lines <span class="elsevierStyleItalic">in vitro</span> and in an animal tumor model <span class="elsevierStyleItalic">in vivo</span><a class="elsevierStyleCrossRef" href="#bib16">16</a>&#44;<a class="elsevierStyleCrossRef" href="#bib20">20</a>&#46; In particular&#44; beta elemene was found to enhance radiosensitivity by influencing the cell cycle distribution of gastric cancer MKN28 cells&#44; and the mechanisms responsible for this effect include the induction of G2&#47;M phase arrest&#44; inhibition of sublethal damage repair&#44; and induction of cell apoptosis&#44; which enhances the killing effects of radioactive rays <a class="elsevierStyleCrossRef" href="#bib21">21</a>&#46; The results of the current study show that the SER<span class="elsevierStyleInf">D0</span> and SER<span class="elsevierStyleInf">Dq</span> values of A549 cells exposed to a low concentration of cytotoxic elemene were greater than 1&#46; In addition&#44; elemene enhanced the sensitivity of A549 cells to radiotherapy&#46; Cellular apoptosis is fundamental to radiotherapy&#44; and its regulatory mechanism plays an important role in cellular radiosensitivity&#46; Apoptosis-related genes such as p53 and Bcl-2 have important regulatory functions in the progression of rapid apoptosis induced by radiation therapy&#46; For instance&#44; a previous study showed that the levels of the antiapoptotic genes Bcl-2 and Bcl-xl in A549 cells decreased&#44; while p53 expression and the production of exosomes increased&#44; following elemene treatment <a class="elsevierStyleCrossRef" href="#bib22">22</a>&#46; This result demonstrates that both p53 and Bcl-2 have important regulatory actions in cervical cancer cell apoptosis induced by radiation&#46; A number of experimental studies have further shown that elemene is involved in regulating the expression of Bax&#44; c-myc&#44; p53&#44; poly &#40;ADP-ribose&#41; polymerase &#40;PARP&#41;&#44; survivin&#44; and livin as well as inducing tumor cell apoptosis <a class="elsevierStyleCrossRef" href="#bib23">23</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib26">26</a>&#46; Our results showed that&#44; compared with the exposure alone group&#44; the group that received elemene combined with irradiation exhibited increased p53 gene expression and significantly decreased Bcl-2 gene expression&#44; and the expression of both genes was significantly correlated&#46; Furthermore&#44; elemene was shown to regulate expression of the apoptosis-related genes Bcl-2 and p53 and induce A549 cell apoptosis&#44; thereby increasing cell radiosensitivity&#46;</p><p id="para230" class="elsevierStylePara elsevierViewall">Interestingly&#44; when Bcl-2 and p53 gene expression was significantly altered&#44; DNA-PKcs protein expression was significantly decreased in the combined treatment group&#46; This result indicates that elemene is also involved in regulating DNA damage repair pathways&#46; Protein kinase activation leads to the phosphorylation of downstream DNA repair proteins&#44; which initiate DNA chain fracture repair <a class="elsevierStyleCrossRef" href="#bib27">27</a>&#44; and the relationship between DNA-PKcs and radiotherapy sensitivity has been a topic of significant research in recent years&#46; It is well established that inhibiting tumor cell expression of DNA-PKcs increases radiation sensitivity&#46; Panet al&#46; <a class="elsevierStyleCrossRef" href="#bib28">28</a> studied the relationship between DNA-PKcs expression and radiation sensitivity in non-small cell lung cancer cell lines&#44; and in adenocarcinomas and large cell carcinomas&#44; DNA-PKcs was shown to be an important component regulating cellular radiosensitivity&#46; This result indicates that DNA-PKcs may be predictive of non-small cell lung cancer cell radiosensitivity&#46; Zou et al&#46; <a class="elsevierStyleCrossRef" href="#bib29">29</a> silenced the DNA-PKcs gene of human mammary epithelial cells &#40;MCF10F&#41; using small interfering RNA &#40;siRNA&#41; technology&#46; Simultaneously&#44; the expression of DNA repair-related proteins&#44; such as DNA-PKcs&#44; Ku80&#44; ATM&#44; and p53&#44; was decreased in these cells&#44; while their sensitivity increased with low doses of radiation&#46; Small molecule inhibitors of DNA-PKcs were also shown to enhance radiation sensitivity of cervical cancer cells <a class="elsevierStyleCrossRef" href="#bib30">30</a>&#46; Our experimental results showed that elemene inhibited DNA-PKcs expression in A549 cells&#44; reduced DNA damage repair&#44; and increased cellular radiosensitivity&#46;</p><p id="para240" class="elsevierStylePara elsevierViewall">DNA-PKcs is a protein with a wide range of functions and is involved in DNA damage repair&#44; apoptosis&#44; and V&#40;D&#41;J recombination <a class="elsevierStyleCrossRef" href="#bib31">31</a>&#46; Yu et al&#46; <a class="elsevierStyleCrossRef" href="#bib32">32</a> found that in non-small cell lung cancer&#44; high expression of DNA-PKcs increased the activity of the DNA damage repair system&#46; In addition&#44; apoptosis inhibition caused by mutant p53 and Bcl-2 expression exhibited a combined effect&#44; which may explain the development of resistance to radiotherapy in small-cell lung cancer&#46; Daido et al&#46; <a class="elsevierStyleCrossRef" href="#bib33">33</a> indicated that following exposure to low doses of radiation&#44; human malignant glioma M059J cells that lack DNA-PKcs underwent massive autophagic cell death that was significantly increased after exposure to DNA-PKcs inhibitors&#46; Furthermore&#44; DNA-PKcs inhibitors exert radiotherapy-sensitizing effects on glioma cells by enhancing type II programmed cell death&#46; Lee et al&#46; <a class="elsevierStyleCrossRef" href="#bib34">34</a> found that p53-inducible gene 3 &#40;PIG3&#41; is involved in apoptosis caused by p53 activation and that this molecule can regulate DNA-PKcs expression&#46; Moreover&#44; knockdown of PIG3 was shown to decrease the level of DNA-PKcs in cells&#46; Our study further addressed the correlation between DNA-PKcs&#44; Bcl-2&#44; and p53 expression&#44; and the results showed that DNA-PKcs expression was significantly positively correlated with that of Bcl-2 &#40;r&#61;0&#46;755&#44; <span class="elsevierStyleItalic">p&#60;</span>0&#46;05&#41; and significantly negatively correlated with p53 &#40;r&#61;0&#46;569&#44; <span class="elsevierStyleItalic">p</span>&#60;0&#46;05&#41;&#46; We further showed that DNA-PKcs was closely related to apoptosis and that elemene increased apoptosis of A549 cells and strengthened cellular radiosensitivity by inhibiting DNA-PKcs expression&#46;</p><p id="para250" class="elsevierStylePara elsevierViewall">In summary&#44; elemene exhibits radiotherapy-sensitizing effects on lung adenocarcinoma A549 cells&#44; and its mechanism of action involves the upregulation of p53 and downregulation of Bcl-2 to promote cell apoptosis&#44; as well as the downregulation of DNA-PKcs to inhibit DSB repair&#46; However&#44; the specific mechanism of action of elemene requires further elucidation&#46;</p></span><span id="cesec200" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle250">AUTHOR CONTRIBUTIONS</span><p id="para260" class="elsevierStylePara elsevierViewall">Zou K&#44; Zhang Z and Zou L designed the research study and wrote the paper&#46; Zou K and Liu C performed the research&#46; Zou K and Zhang Z analyzed the data&#46;</p></span></span>"
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        1 => array:2 [
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          "titulo" => "INTRODUCTION"
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          "titulo" => "MATERIALS AND METHODS"
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              "titulo" => "Cell culture"
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            1 => array:2 [
              "identificador" => "cesec40"
              "titulo" => "Reagents and instruments"
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              "identificador" => "cesec50"
              "titulo" => "Irradiation conditions"
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            3 => array:2 [
              "identificador" => "cesec60"
              "titulo" => "Clonogenic assay"
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            4 => array:2 [
              "identificador" => "cesec70"
              "titulo" => "Morphological assessment of apoptosis"
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            5 => array:2 [
              "identificador" => "cesec80"
              "titulo" => "Apoptosis standard"
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              "identificador" => "cesec90"
              "titulo" => "Assessment of apoptosis"
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              "identificador" => "cesec100"
              "titulo" => "Neutral comet assay"
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              "titulo" => "Western blot assay"
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              "titulo" => "Statistical analysis"
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          "titulo" => "RESULTS"
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              "identificador" => "cesec140"
              "titulo" => "Effects of elemene on cell radiosensitivity"
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            1 => array:2 [
              "identificador" => "cesec150"
              "titulo" => "Effect of elemene on A549 cell apoptosis"
            ]
            2 => array:2 [
              "identificador" => "cesec160"
              "titulo" => "Effect of elemene on DSB repair in A549 cells"
            ]
            3 => array:2 [
              "identificador" => "cesec170"
              "titulo" => "Effects of elemene on DNA-PKcs&#44; Bcl-2&#44; and p53 protein expression in A549 cells"
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              "identificador" => "cesec180"
              "titulo" => "Protein expression correlation analysis"
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          "titulo" => "DISCUSSION"
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          "titulo" => "AUTHOR CONTRIBUTIONS"
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          "titulo" => "ACKNOWLEDGEMENT"
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          "titulo" => "REFERENCES"
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    "fechaRecibido" => "2015-01-06"
    "fechaAceptado" => "2015-06-01"
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          "clase" => "keyword"
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            0 => "Elemene"
            1 => "Radiosensitivity"
            2 => "A549 cells"
            3 => "DNA-PKcs"
            4 => "Bcl-2"
            5 => "p53"
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        "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJECTIVE&#58;</span><p id="spara70" class="elsevierStyleSimplePara elsevierViewall">To investigate the effect of elemene on the radiosensitivity of A549 cells and its possible molecular mechanism&#46;</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">METHODS&#58;</span><p id="spara80" class="elsevierStyleSimplePara elsevierViewall">Apoptosis of A549 cells was detected by flow cytometry and fluorescence microscopy&#46; The effect of double-strand break &#40;DSB&#41; damage repair in A549 cells was evaluated using the neutral comet assay&#46; Protein expression levels were detected using western blotting&#44; and the correlation between protein levels was analyzed&#46;</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">RESULTS&#58;</span><p id="spara90" class="elsevierStyleSimplePara elsevierViewall">Elemene exhibited a radiosensitizing effect on A549 cells&#46; The level of apoptosis induced by elemene combined with radiation was significantly greater &#40;<span class="elsevierStyleItalic">p&#60;</span>0&#46;01&#41; than that elicited by either radiation or elemene alone&#46; Following radiation and subsequent repair for 24 h&#44; the tail intensity of A549 cells treated with a combination of elemene and radiation was greater than that of cells treated with either elemene or radiation alone &#40;<span class="elsevierStyleItalic">p</span>&#60;0&#46;01&#41;&#46; This result indicates that elemene inhibits cellular DSB repair&#46; Both elemene combined with radiation and radiation alone decreased the protein expression of DNA-PKcs and Bcl-2 compared to elemene alone &#40;<span class="elsevierStyleItalic">p&#60;</span>0&#46;01&#41;&#44; while p53 protein expression was increased &#40;<span class="elsevierStyleItalic">p</span>&#60;0&#46;01&#41;&#46; A negative correlation was observed between DNA-PKcs and p53 expression &#40;r&#61;-0&#46;569&#44; <span class="elsevierStyleItalic">p</span>&#61;0&#46;040&#41;&#44; while a positive correlation was found between DNA-PKcs and Bcl-2 expression &#40;r&#61;0&#46;755&#44; <span class="elsevierStyleItalic">p</span>&#61;0&#46;012&#41;&#46;</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">CONCLUSIONS&#58;</span><p id="spara100" class="elsevierStyleSimplePara elsevierViewall">Elemene exhibits a radiosensitizing effect on A549 cells&#44; and its underlying molecular mechanism of action may be related to the downregulation of DNA-PKcs gene expression&#46;</p></span>"
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            "titulo" => "RESULTS&#58;"
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        "nota" => "<p class="elsevierStyleNotepara" id="cenpara10">No potential conflict of interest was reported&#46;</p>"
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          "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Cell survival curves of A549 cells following treatment with 0&#44; 10 or 20 &#181;g&#47;mL elemene and exposure to x-ray doses from 0 to 10 Gy&#46;</p>"
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          "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Elemene induces apoptosis in A549 cells&#46; Cells were incubated with 10 or 20 &#956;g&#47;mL elemene for 24 h&#44; followed by irradiation with 4 Gy X-rays and washing with PBS&#46; <span class="elsevierStyleBold">&#40;A&#41;</span> Cells were imaged with an Olympus BX-51 fluorescent microscope using appropriate filter cubes&#46; <span class="elsevierStyleBold">&#40;B&#41;</span> Chromatin condensation was analyzed by fluorescence microscopy after DNA staining with Hoechst 3334&#46; The results are expressed as the mean &#177; SD of three independent experiments&#44; n&#61;3&#44; <span class="elsevierStyleSup">&#42;&#42;</span><span class="elsevierStyleItalic">p&#60;</span>0&#46;01 compared to control&#44; <span class="elsevierStyleSup">&#35;&#35;</span><span class="elsevierStyleItalic">p&#60;</span>0&#46;01 compared to radiation alone&#46;</p>"
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        "identificador" => "fig3"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 442
            "Ancho" => 772
            "Tamanyo" => 38788
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">Influence of elemene on radiation-induced DSB&#46; A549 cells were irradiated with 4 Gy X-rays in the absence or presence of elemene &#40;10 or 20 &#956;g&#47;mL&#41; and assayed immediately after radiation or returned to the incubator for 24 h to permit repair&#46; Comet assays were performed immediately after incubation with elemene treatment&#44; irradiation&#44; or combination treatment&#46; Columns represent the means of the tail moments from three independent experiments&#44; and the bars represent the SD&#44; <span class="elsevierStyleSup">&#42;&#42;</span><span class="elsevierStyleItalic">p&#60;</span>0&#46;01 vs&#46; control&#44; <span class="elsevierStyleSup">&#35;&#35;</span><span class="elsevierStyleItalic">p&#60;</span>0&#46;01 compared to radiation alone&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig4"
        "etiqueta" => "Figure 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 973
            "Ancho" => 780
            "Tamanyo" => 88632
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Western blot analysis of the protein levels of Bcl-2&#44; p53 and DNA-PKcs&#46; A549 cells were irradiated with 4 Gy X-rays following treatment with 10 or 20 &#956;g&#47;mL elemene for 24 h&#46; Proteins were extracted and separated by SDS-PAGE&#46; <span class="elsevierStyleBold">&#40;A&#41;</span> Levels of Bcl-2&#44; p53 and DNA-PKcs were quantitated by densitometry&#44; and the ratios of the three proteins are displayed&#46; Values represent the mean &#177; SD&#44; n&#61;3&#44; <span class="elsevierStyleSup">&#42;&#42;</span><span class="elsevierStyleItalic">p&#60;</span>0&#46;01 compared to the control&#44; <span class="elsevierStyleSup">&#35;&#35;</span><span class="elsevierStyleItalic">p&#60;</span>0&#46;01 compared to radiation alone&#46; Elemene inhibited the protein expression of <span class="elsevierStyleBold">&#40;B&#41;</span> DNA-PKcs and <span class="elsevierStyleBold">&#40;C&#41;</span> Bcl-2 and promoted the protein expression of p53&#46; Key&#58; 1&#44; Control&#59; 2&#44; irradiation&#59; 3&#44; 10 &#956;g&#47;mL&#59; 4&#44; 20 &#956;g&#47;mL&#59; 5&#44; 10 &#956;g&#47;mL &#43; irradiation&#59; 6&#44; 20 &#956;g&#47;mL &#43; irradiation&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "tbl1"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="tfn1" class="elsevierStyleSimplePara elsevierViewall">Cells were incubated with 10 or 20 &#956;g&#47;mL concentrations of elemene for 24 h and were then irradiated with 0&#44; 2&#44; 4&#44; 6&#44; 8&#44; and 10 Gy and cultured for another 14 days&#46; The number of cells forming more than 50 clones was counted under the inverted microscope to calculate the cloning efficiency &#40;CE&#41;&#58; CE &#40;&#37;&#41;&#61;&#40;Clone formation average of treatment group&#47;inoculated cell number&#41; &#215; 100&#37;&#46; Survival fraction &#40;SF&#41;&#61;&#40;irritated group CE&#47;non-irradiated group PE&#41; &#215; 100&#37;&#46; The experiment was repeated 3 times to calculate the average&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">0 Gy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">2 Gy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">4 Gy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">6 Gy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">8 Gy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">10 Gy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">84&#46;1&#177;13&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">70&#46;2&#177;10&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">66&#46;3&#177;1&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">47&#46;3&#177;2&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">26&#46;0&#177;1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">10 &#956;g&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">97&#46;7&#177;20&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">76&#46;2&#177;10&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">49&#46;5&#177;6&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">22&#46;5&#177;2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">7&#46;5&#177;1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">3&#46;4&#177;0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">20 &#956;g&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">95&#46;4&#177;18&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">63&#46;6&#177;7&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">30&#46;4&#177;3&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">5&#46;7&#177;1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">2&#46;7&#177;0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">0&#46;7&#177;0&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara50" class="elsevierStyleSimplePara elsevierViewall">Survival fraction &#40;&#37;&#41;&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "tbl2"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="tfn2" class="elsevierStyleSimplePara elsevierViewall">SPSS17&#46;0 was used to calculate survival parameters including SF2 &#40;surviving fraction of 2 Gy&#41;&#44; D<span class="elsevierStyleInf">0</span> &#40;mean lethal dose or final slope&#41;&#44; and Dq &#40;quasi-thres-hold dose&#41;&#46; SER &#40;sensitization enhancement ratio&#41;&#46; SER D<span class="elsevierStyleInf">0</span> &#40;Dq&#41;&#61;control group D<span class="elsevierStyleInf">0</span> &#40;Dq&#41;&#47;drug group D<span class="elsevierStyleInf">0</span> &#40;Dq&#41;&#46; Three parallel samples were set at each radiation dosage&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col"><span class="elsevierStyleItalic">D</span><span class="elsevierStyleInf">0</span> &#40;Gy&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
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                  \t\t\t\t  " align="center" valign="middle" scope="col"><span class="elsevierStyleItalic">D</span><span class="elsevierStyleInf">q</span> &#40;Gy&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="middle" scope="col">SF<span class="elsevierStyleInf">2</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">SER<span class="elsevierStyleInf"><span class="elsevierStyleItalic">D</span>0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">SER<span class="elsevierStyleInf"><span class="elsevierStyleItalic">D</span>q</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="middle">Control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">2&#46;54&#177;0&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">2&#46;68&#177;0&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">84&#46;6&#177;20&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">10 &#956;g&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;64&#177;0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;87&#177;0&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">56&#46;3&#177;14&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;54&#177;0&#46;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;43&#177;0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">20 &#956;g&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;55&#177;0&#46;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;53&#177;0&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">43&#46;2&#177;10&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;63&#177;0&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;75&#177;0&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara60" class="elsevierStyleSimplePara elsevierViewall">Radiation parameters for a single-hit multi-target model&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "REFERENCES"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec10"
          "bibliografiaReferencia" => array:34 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung cancer&#46; Radiotherapy in lung cancer&#58; Actual methods and future trends"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              A Maciejczyk \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              I Skrzypczynska \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              M Janiszewska \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rpor.2014.04.012"
                      "Revista" => array:7 [
                        "tituloSerie" => "Rep Pract Oncol Radiother"
                        "fecha" => "2014"
                        "volumen" => "19"
                        "numero" => "6"
                        "paginaInicial" => "353"
                        "paginaFinal" => "360"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25337407"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/j.rpor.2014.04.012"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;j&#46;rpor&#46;2014&#46;04&#46;012"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib2"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Enhanced radiation and chemotherapy-mediated cell killing of human cancer cells by small inhibitory RNA silencing of DNA repair factors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              SJ Collis \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              MJ Swartz \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              WG Nelson \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              TL DeWeese \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Cancer Res"
                        "fecha" => "2003"
                        "volumen" => "63"
                        "numero" => "7"
                        "paginaInicial" => "1550"
                        "paginaFinal" => "1554"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12670903"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib3"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evidence for the involvement of DNA-dependent protein kinase in the phenomena of low dose hyper-radiosensitivity and increased radioresistance"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              B Marples \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              NE Cann \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              CR Mitchell \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              PJ Johnston \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              MC Joiner \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1080/09553000210166606"
                      "Revista" => array:7 [
                        "tituloSerie" => "Int J Radiat Biol"
                        "fecha" => "2002"
                        "volumen" => "78"
                        "numero" => "12"
                        "paginaInicial" => "1139"
                        "paginaFinal" => "1147"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12556341"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1080/09553000210166606"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1080&#47;09553000210166606"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib4"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Selective inactivation of DNA-dependent protein kinase with antisense oligodeoxynucleotides&#58; consequences for the rejoining of radiation-induced DNA double-strand breaks and radiosensitivity of human cancer cell lines"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              A Sak \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              M Stuschke \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              R Wurm \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              G Schroeder \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              B Sinn \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              G Wolf \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Cancer Res"
                        "fecha" => "2002"
                        "volumen" => "62"
                        "numero" => "22"
                        "paginaInicial" => "6621"
                        "paginaFinal" => "6624"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12438258"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib5"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sensing and repairing DNA double-strand breaks"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              SP Jackson \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1093/carcin/23.5.687"
                      "Revista" => array:7 [
                        "tituloSerie" => "Carcinogenesis"
                        "fecha" => "2002"
                        "volumen" => "23"
                        "numero" => "5"
                        "paginaInicial" => "687"
                        "paginaFinal" => "696"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12016139"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1093/carcin/23.5.687"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1093&#47;carcin&#47;23&#46;5&#46;687"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib6"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Apoptosis as a predictor of paclitaxel-induced radiosensitization in human tumor cell lines"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              B Kurdoglu \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              N Cheong \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              J Guan \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              BW Corn \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              WJ Curran Jr \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              G Iliakis \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Cancer Res"
                        "fecha" => "1999"
                        "volumen" => "5"
                        "numero" => "9"
                        "paginaInicial" => "2580"
                        "paginaFinal" => "2587"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10499636"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib7"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Apotosis and Radiosensitivity of Cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              LP Wang \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              K Liang \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Foreign Medical Science"
                        "fecha" => "2000"
                        "volumen" => "24"
                        "numero" => "2"
                        "paginaInicial" => "75"
                        "paginaFinal" => "78"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib8"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The molecular and cellular basis of radiosensitivity&#58; implications for understanding how normal tissues and tumors respond to therapeutic radiation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              EM Rosen \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              S Fan \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              S Rockwell \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              ID Goldberg \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Cancer Invest"
                        "fecha" => "1999"
                        "volumen" => "17"
                        "numero" => "1"
                        "paginaInicial" => "56"
                        "paginaFinal" => "72"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10999050"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;3109&#47;07357909909011718"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib9"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biological basis of radiation sensitivity&#46; Part 2&#58; Cellular and molecular determinants of radiosensitivity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              EM Rosen \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              S Fan \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              ID Goldberg \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              S Rockwell \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Oncology &#40;Williston Park&#41;"
                        "fecha" => "2000"
                        "volumen" => "14"
                        "numero" => "5"
                        "paginaInicial" => "741"
                        "paginaFinal" => "757"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10853463"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "In vitro study of radiosensitization of &#946;-elemene in A549 cell line from denocarcinoma of lung"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              H Jiang \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              S Ma \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              J Feng \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chinese-German J of Clin Oncol"
                        "fecha" => "2009"
                        "volumen" => "8"
                        "numero" => "1"
                        "paginaInicial" => "12"
                        "paginaFinal" => "15"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1007&#47;s10330-008-0139-3"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Down regulation of mammalian target of rapamycin decreases HIF-1&#945; and survivin expression in anoxic lung adenocarcinoma A549 cell to elemene and&#47;or irradiation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              K Zou \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              E Tong \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              Y Xu \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              X Deng \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              L Zou \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Tumor Biol"
                        "fecha" => "2014"
                        "volumen" => "35"
                        "numero" => "10"
                        "paginaInicial" => "9735"
                        "paginaFinal" => "9741"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1007&#47;s13277-014-2226-0"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The variation of gene expression profile in radiosensitivity to kidney cancer cells induced by elemenen"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              W Cheng \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              JP Li \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              ZM Wang \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              W Song \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              C Huang \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chin J Urol"
                        "fecha" => "2007"
                        "volumen" => "28"
                        "numero" => "2"
                        "paginaInicial" => "87"
                        "paginaFinal" => "90"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A Study of Radiosensitivity of &#946;-Elemene to Squamous Cell Carcinoma of Tongue Tca-8113 Cell Line in Vitro"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              DP Wu \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              XM Li \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JF Zhao \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              HB Wang \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              DQ Zhao \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Journal of Basic and Clinical Oncology"
                        "fecha" => "2006"
                        "volumen" => "19"
                        "numero" => "2"
                        "paginaInicial" => "116"
                        "paginaFinal" => "117"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The study of the &#946;-elemene effect on the augment of radiation treatment in mouse inoculated U14 strain"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              LJ Zou \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              XH Sun \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              XY Xu \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chin J Radiological Medicine and Protection"
                        "fecha" => "2004"
                        "volumen" => "24"
                        "numero" => "3"
                        "paginaInicial" => "254"
                        "paginaFinal" => "255"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Radiosensitization of beta-elemene on VX2 carcinoma transplanted on kidney in rabbits in vivo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              JJ She \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              ZM Wang \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              XM Che \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              CE Pan \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.3736/jcim20060415"
                      "Revista" => array:7 [
                        "tituloSerie" => "Zhong Xi Yi Jie He Xue Bao"
                        "fecha" => "2006"
                        "volumen" => "4"
                        "numero" => "4"
                        "paginaInicial" => "392"
                        "paginaFinal" => "396"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16834978"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.3736/jcim20060415"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;3736&#47;jcim20060415"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "&#946;-Elemene radiosensitizes lung cancer A549 cells by enhancing DNA damage and inhibiting DNA repair"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              LJ Li \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              LF Zhong \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              LP Jiang \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              CY Geng \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              LJ Zou \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1002/ptr.3367"
                      "Revista" => array:7 [
                        "tituloSerie" => "Phytother Res"
                        "fecha" => "2011"
                        "volumen" => "25"
                        "numero" => "7"
                        "paginaInicial" => "1095"
                        "paginaFinal" => "1097"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22692988"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1002/ptr.3367"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1002&#47;ptr&#46;v25&#46;7"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Survival and tumour control probability in tumours withheterogeneous oxygenation&#58; A comparison between the linearquadratic and the universal survival curve models for high doses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              E Lindblom \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              A Dasu \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              I Lax \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              I Toma-Dasu \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.3109/0284186X.2014.925582"
                      "Revista" => array:7 [
                        "tituloSerie" => "Acta Oncol"
                        "fecha" => "2014"
                        "volumen" => "53"
                        "numero" => "8"
                        "paginaInicial" => "1035"
                        "paginaFinal" => "1040"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24957551"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.3109/0284186X.2014.925582"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;3109&#47;0284186X&#46;2014&#46;925582"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Variation in the measurement of DNA damage by comet assay measured by the ECVAG inter-laboratory validation trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              L Forchhammer \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              C Johansson \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              S Loft \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              L Moller \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              RW Godschalk \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              SA Langie \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1093/mutage/gep048"
                      "Revista" => array:7 [
                        "tituloSerie" => "Mutagenesis"
                        "fecha" => "2010"
                        "volumen" => "25"
                        "numero" => "2"
                        "paginaInicial" => "113"
                        "paginaFinal" => "123"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19910383"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1093/mutage/gep048"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1093&#47;mutage&#47;gep048"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The lysosomal-mitochondrial axis in free fatty acid-induced hepatic lipotoxicity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              Z Li \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              M Berk \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              TM McIntyre \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              GJ Gores \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              AE Feldstein \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.22183"
                      "Revista" => array:7 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2008"
                        "volumen" => "47"
                        "numero" => "5"
                        "paginaInicial" => "1495"
                        "paginaFinal" => "1503"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18220271"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1002/hep.22183"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1002&#47;&#40;ISSN&#41;1527-3350"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Down-regulation of survivin and hypoxia-inducible factor-1 alpha by beta-elemene enhances the radiosensitivity of lung adenocarcinoma xenograft"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              G Li \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              B Xie \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              X Li \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              Y Chen \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              Q Wang \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              Y Xu \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1089/cbr.2011.1003"
                      "Revista" => array:7 [
                        "tituloSerie" => "Cancer Biother Radiopharm"
                        "fecha" => "2012"
                        "volumen" => "27"
                        "numero" => "1"
                        "paginaInicial" => "56"
                        "paginaFinal" => "64"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22248028"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1089/cbr.2011.1003"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1089&#47;cbr&#46;2011&#46;1003"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Enhancement of gastric cancer MKN28 cell line radiosensitivity induced by beta-elemene"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              S He \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              J Liu \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              Z Zhang \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              X Che \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              L Fan \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              S Chang \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Zhonghua Wai Ke Za Zhi"
                        "fecha" => "2014"
                        "volumen" => "52"
                        "numero" => "6"
                        "paginaInicial" => "442"
                        "paginaFinal" => "445"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25219560"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib22"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "&#946;-Elemene against human lung cancer via up-regulation of P53 protein expression to promote the release of exosome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              J Li \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              A JunYu&#44; Liu \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              Y Wang \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/j.lungcan.2014.08.015"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lung Cancer"
                        "fecha" => "2014"
                        "volumen" => "86"
                        "numero" => "2"
                        "paginaInicial" => "144"
                        "paginaFinal" => "150"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25204604"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/j.lungcan.2014.08.015"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;j&#46;lungcan&#46;2014&#46;08&#46;015"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib23"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effects of &#946;-elemene on the activation of Akt and the expressions of apoptosis-related proteins in gastric cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              Y Zhang \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              MF Zhao \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              YP Liu \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Shanxi Oncology Medicine"
                        "fecha" => "2012"
                        "volumen" => "3"
                        "paginaInicial" => "451"
                        "paginaFinal" => "454"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib24"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Influence on apoptosis relevant protein expression of human lung adenocarcinoma A549 cell line managed by Elemene"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              XQ Zhou \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              XJ Qiu \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              HY Zhao \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Journal of Modern Oncology"
                        "fecha" => "2012"
                        "volumen" => "20"
                        "numero" => "10"
                        "paginaInicial" => "2027"
                        "paginaFinal" => "2030"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib25"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Study on inhibition of the expression of c-myc gene of human glioma U251cell line and the effect mechanism of effect on cellular apoptosis by elemene"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              WZ Yang \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              CM Chen \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              SS Shi \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chin J Clin Oncol"
                        "fecha" => "2005"
                        "volumen" => "32"
                        "numero" => "13"
                        "paginaInicial" => "763"
                        "paginaFinal" => "766"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib26"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of &#946;-elemene combined with radiotherapy on the expression of Livin mRNA and apoptosis of lung adenocarcinoma cell line A549"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              QT Zhao \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              Y Yang \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              CB Sun \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Journal of Modern Oncology"
                        "fecha" => "2013"
                        "volumen" => "21"
                        "numero" => "2"
                        "paginaInicial" => "257"
                        "paginaFinal" => "260"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib27"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              P Calsou \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              C Delteil \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              P Frit \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              J Drouet \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              B Salles \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/s0022-2836(02)01328-1"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Mol Biol"
                        "fecha" => "2003"
                        "volumen" => "326"
                        "numero" => "1"
                        "paginaInicial" => "93"
                        "paginaFinal" => "103"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12547193"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/s0022-2836(02)01328-1"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;S0022-2836&#40;02&#41;01328-1"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib28"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Correlation of DNA-dependent protein kinase catalytic subunit expression to radiosensitivity of non-small cell lung cancer cell lines"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              Y Pan \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              WX Li \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JM Li \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              JQ Zhu \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              YQ Liang \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              AL Guo \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.5732/cjc.009.10013"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ai Zheng"
                        "fecha" => "2009"
                        "volumen" => "28"
                        "numero" => "7"
                        "paginaInicial" => "714"
                        "paginaFinal" => "717"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19624897"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib29"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "DNA-PKcs silencing inhibit the DNA repair induced by low dose radiation on human breast epithelial cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              W Zou \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              J Che \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              CJ Wang \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chin J Biotech"
                        "fecha" => "2009"
                        "volumen" => "25"
                        "numero" => "5"
                        "paginaInicial" => "727"
                        "paginaFinal" => "732"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib30"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhibition of DNA-PKcs by siRNA and its effect on the growth of HeLa cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              J An \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              JL Sui \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              QZ Xu \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4269/ajtmh.21-1184"
                      "Revista" => array:7 [
                        "tituloSerie" => "Carcinogenesis&#44; Teratogenesis &#38; Mutagenesis"
                        "fecha" => "2005"
                        "volumen" => "17"
                        "numero" => "6"
                        "paginaInicial" => "327"
                        "paginaFinal" => "331"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35895428"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib31"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mechanism of non-homologous end joing and its bilolgical implications"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              YQ Yan \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              PK Zhou \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Journal of Medical Molecular Biology"
                        "fecha" => "2006"
                        "volumen" => "3"
                        "numero" => "1"
                        "paginaInicial" => "69"
                        "paginaFinal" => "72"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib32"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
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                              \t\t\t\t\t\t\t\t
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                      "titulo" => "Inhibition of the DNA-dependent protein kinase catalytic subunit radiosensitizes malignant glioma cells by inducing autophagy"
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                              S Daido \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              A Yamamoto \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              K Fujiwara \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              R Sawaya \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              S Kondo \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              Y Kondo \n
                              \t\t\t\t\t\t\t\t
                              """
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                        ]
                      ]
                    ]
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                        "tituloSerie" => "Cancer Res"
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                        "paginaFinal" => "4375"
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                          0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "The p53-inducible gene 3 &#40;PIG3&#41; contributes to early cellular response to DNA damage"
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                              JH Lee \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              Y Kang \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              V Khare \n
                              \t\t\t\t\t\t\t\t
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                            3 => """
                              ZY Jin \n
                              \t\t\t\t\t\t\t\t
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                            4 => """
                              MY Kang \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              Y Yoon \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
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                        "tituloSerie" => "Oncogene"
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                        "numero" => "10"
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                        "paginaFinal" => "1450"
                        "link" => array:1 [
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Article information

ISSN: 18075932
Original language: English

DOI:10.6061/clinics/2015(08)05

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Year/Month	Html	Pdf	Total

2024 November	2	3	5
2024 October	13	22	35
2024 September	19	20	39
2024 August	14	14	28
2024 July	18	21	39
2024 June	14	10	24
2024 May	35	14	49
2024 April	28	8	36
2024 March	45	12	57
2024 February	41	13	54
2024 January	12	13	25
2023 December	9	19	28
2023 November	15	16	31
2023 October	9	17	26
2023 September	5	14	19
2023 August	4	2	6
2023 July	7	6	13
2023 June	16	0	16
2023 May	28	0	28
2023 April	31	2	33
2023 March	30	3	33
2023 February	16	1	17
2023 January	2	2	4
2022 December	12	2	14

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