Induction of sensitivity to ganciclovir in human hepatocellular carcinoma cells by adenovirus-mediated gene transfer of herpes simplex virus thymidine kinase
Qian C, Bilbao R, Bruña O, Prieto J.
Department of Internal Medicine, School of Medicine, University of Navarra, Pamplona, Spain
Date: Jul 1, 1995Hepatology
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 vitro by a recombinant adenovirus carrying lacZ reporter gene (AdCMVlacZ). Expression of HSV-tk in HCC cells infected with a recombinant adenovirus carrying HSV-tk gene (AdCMVtk) induced sensitivity to ganciclovir in a dose-dependent 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 vitro. 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.
CITATION Hepatology. 1995 Jul;22(1):118-23
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