Induction of sensitivity to ganciclovir in human hepatocellular carcinoma cells by adenovirus-mediated gene transfer of herpes simplex virus thymidine kinase

✍ Scribed by Cheng Qian; Roberto Bilbao; Oscar Bruña; Jesús Prieto

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 694 KB
• Volume: 22
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840220119

✦ Synopsis

We have analyzed the ability of a recombinant replication-defective adenovirus to transfer the thymidine kinase gene of herpes simplex virus (HSV-tk) into hepatocellular carcinoma (HCC) cells to confer sensitivity to ganciclovir. Three HCC cell lines (Hep3B, PLC/PRF/5, and HepG2) were efficiently infected in uitro by a recombinant adenovirus carrying lacZ reporter gene (Ad-CMVlacZ). Expression of HSV-tk in HCC cells infected with a recombinant adenovirus carrying HSV-tk gene (AdCMVtk) induced sensitivity to ganciclovir in a dosedependent manner. A bystander killing effect was observed when 90% of uninfected tumor cells were mixed with only 10% of AdCMVtk-infected cells. These data show that recombinant adenoviruses are efficient vectors for transduction of drug-sensitizing genes to HCC cells in uitro. We suggest that a gene therapy approach to hepatocellular carcinoma can be established using adenoviral transfer of HSV-tk to tumor cells and subsequent administration of ganciclovir. (HEPATOLOGY 1995; 22:118-123.)

Hepatocellular carcinoma (HCC) is a common human malignancy that resists conventional chemotherapy and radi~therapy.'.~ Modifications of chemotherapy, such as intrahepatic artery infusion of cytotoxic drugs, improve tumor responses but do not substantially affect patient

The best chance for cure is complete surgical ablation of the tumor by partial hepatectomy or by total hepatectomy combined with liver transplantation, but these procedures are appropriate only in a minority of Thus, HCC remains one of the most difficult tumors to treat.

Progress in molecular biology has recognized a num-Abbreviations: HCC, hepatocellular carcinoma; HSV-tk, thymidine kinase of herpes simplex virus; GCV, ganciclovir; CMV, cytomegalovirus; moi, multiplicity of infection.