Retrovirus-mediated herpes simplex virus thymidine kinase gene therapy approach for hepatocellular carcinoma

The therapeutic effect of herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system on hepatocellular carcinoma was studied in this experiment. The tk-containing retroviral recombinants were used to infect hepatoma cells (BEL-7402) and the cells were treated with ganciclovir (0-1000 mu g/ml). The results showed that HSV-tk gene could be efficiently transferred in vitro into hepatoma cells and stably expressed. The growth potential of the tk-containing cells was significantly inhibited by GCV (P < 0.01) as compared to the non-tk-containing cells. The antitumor effect of HSV-tk/GCV system was also produced ex vivo in tk-containing tumor of nude mice as characterized by a marked decrease in tumor growth after GCV treatment contrary to a progressive enlargement of non-tk-containing tumors. Although the histological examination demonstrated that the efficiency of the gene transfer was less than 30%, the killing effect of HSV-tk/GCV system on hepatocellular carcinoma was still significantly generated. The proper mechanism of HSV-tk gene therapy on hepatic tumor referred as "bystander effect" in therapeutic approach has not been found in this study and required to be explored further.