Induction of sensitivity to ganciclovir in human hepatocellular carcinoma cells by adenovirus-mediated gene transfer of herpes simplex virus thymidine kinase.
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.
Qian
C
C
Department of Internal Medicine, School of Medicine, University of Navarra, Pamplona, Spain.
Bilbao
R
R
Bruña
O
O
Prieto
J
J
D000256:Adenoviridae / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D004351:Drug Resistance / Q000235:genetics; D015774:Ganciclovir / Q000494:pharmacology* / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D018139:Simplexvirus / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics*; D014407:Tumor Cells, Cultured
D013937:Thymidine Kinase; D015774:Ganciclovir