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
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.
CITA DEL ARTÍCULO Hepatology. 1995 Jul;22(1):118-23