Mode of cell death associated with adenovirus-mediated suicide gene therapy in HNSCC tumor model.

BACKGROUND Adenoviral mediated suicide gene therapy has been shown to have a tumoricidal effect against a variety of tumor models. Although the efficacy of this treatment regimen has been verified, the molecular mechanism of Herpes simplex virus thymidine kinase gene (HSVtk)- and ganciclovir (GCV)-induced cell death is still not well established. MATERIALS AND METHODS The mode of cell death by adenoviral (Adv)-HSVtk/GCV was examined in the head and neck squamous cell carcinoma cell line, NT8e. RESULTS The cell death was independent of apoptotic gene expression. Moreover apoptosis was not evident from cell cycle kinetic analysis. Adv-HSVtk/GCV treated cells showed time dependent accumulation of cells in the S-phase of the cell cycle although there was no increase in the "apoptotic peak" or sub-G1 population. Swelling of the cytoplasm without apparent nuclear condensation suggested a possible involvement of necrosis. CONCLUSION The apoptotic mechanism may not play a central role in the Adv-HSVtk/GCV induced NT8e cell death and other mechanisms should be considered.