[Effects of retrovirus-mediated HSV-tk/GCV on human hepatocellular carcinoma].

OBJECTIVE: The efficacy of the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) suicide-gene therapy system on human hepatocellular carcinoma was observed in vitro as well as ex vivo. METHODS: The recombinant retroviral vector containing HSV-tk gene was constructed and HCC9204 human hepatocellular carcinoma cell line was infected with the recombinant retrovirus. Following selection the HCC9204/tk cell line which stably expressed tk was cloned. The sensitivity of HCC9204/tk cells to GCV was examined in vitro. Antitumor effects of GCV were also observed after the administration of GCV in nude mice bearing tumor derived from HCC9204/tk cells. RESULTS: The HSV-tk gene expressed stably in HCC9204/tk cells. In vitro the growth inhibition studies showed that HCC9204/tk cells were highly sensitive to GCV (IC50 1.2 mg/L in 72 hour), and the HSV-tk gene-modified HCC9204/tk cells were toxic to nearby unmodified HCC9204 tumor cells that were resistant to GCV. This phenomenon was termed "bystander effect". Ex vivo studies showed similar results that significant tumor inhibition was found in the treatment group than in control group. CONCLUSION: Tumor cells expressing HSV-tk gene can be eradicated by GCV in vitro and ex vivo. The HSV-tk/GCV suicide-gene therapy system mediated retrovirally may provide an effective approach to treatment of human hepatoma.