Efecto antitumoral del gen suicida hsv-tk y ganciclovir en un modelo experimental de carcinoma epidermoide de cabeza y cuello

Resumen

Introducción

Se estudió la transfección por adenovectores y el efecto antitumoral del gen HVS-tk asociado a ganciclovir (AdCMVtk/GCV) en células KB de carcinoma epidermoide oral humano, in vitro e in vivo.

Material y métodos

La trasfección por adenovectores se comprobó al teñir con X-gal cultivos y cortes tumorales KB tras exponerlos al adenovector AdCMVlacZ. El efecto antitumoral de AdCMVtk/GCV in vitro se estudió al comparar la supervivencia entre cultivos expuestos a AdCMVtk/GCV y a AdCMVlacZ/GCV. Para valorar el efecto antitumoral in vivo, se comparó el volumen de necrosis tumoral con respecto al total, entre animales tratados con AdCMVtk/GCV y con AdCMVlacZ/GCV. Se estudió la toxicidad hepática y renal.

Resultados

In vitro, la supervivencia con AdCMVtk/GCV es menor que con AdCMVlacZ/GCV. In vivo, el volumen de necrosis es mayor con AdCMVtk/GCV que con AdCMVlacZ/GCV. No se constató toxicidad hepática ni renal.

Conclusiones

Las células KB se transfectan por adenovectores y son destruidas por AdCMVtk/GCV, in vitro e in vivo (sin toxicidad en este modelo experimental animal).

Abstract

Introduction

We studied the transfection by adenoviral vectors and the antitumoral effect of HSV-tk gene associated with ganciclovir (AdCMVtk/GCV) in KB human oral cavity squamous cell carcinoma, in vitro and in vivo.

Materials and methods

Transfection was assessed by the X-gal stain. It was used in cell cultures and tumoral sections previously exposed to adenoviral vector AdCMVlacZ. In vitro, in order to study the antitumoral effect of AdCMVtk/GCV, survival of cell cultures exposed to AdCMVtk/GCV and to AdCMVlacZ/ GCV was compared. In vivo, necrotic volume as a percentage of total tumoral volume, was compared between AdCMVtk/GCV treated group and AdCMVlacZ/GCV exposed group. Hepatic and renal toxicities were assessed.

Results

In vitro, survival of cell cultures treated with AdCMVtk/GCV was less than AdCMVlacZ/GCV exposed cells. In vivo, necrotic volume was larger in AdCMVtk/GCV treated group than in AdCMVlacZ/GCV exposed group. No toxicity was found (hepatic, renal).

Conclusions

KB cells are transfected by adenoviral vectors and are killed by AdCMVtk/GCV, both in vitro and in vivo (no toxicity was found in the animal model).