title: Retrovirus-mediated herpes simplex virus thymidine kinase gene therapy approach for hepatocellular carcinoma.
abstract: The therapeutic effect of herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system on hepatocellular carcinoma was studied in this experiment. The tk-containing retroviral recombinants were used to infect hepatoma cells (BEL-7402) and the cells were treated with ganciclovir (0-1000 microg/ml). The results showed that HSV-tk gene could be efficiently transferred in vitro into hepatoma cells and stably expressed. The growth potential of the tk-containing cells was significantly inhibited by GCV (P<0.01) as compared to the non-tk-containing cells. The antitumor effect of HSV-tk/GCV system was also produced ex vivo in tk-containing tumor of nude mice as characterized by a marked decrease in tumor growth after GCV treatment contrary to a progressive enlargement of non-tk-containing tumors. Although the histological examination demonstrated that the efficiency of the gene transfer was less than 30%, the killing effect of HSV-tk/GCV system on hepatocellular carcinoma was still significantly generated. The proper mechanism of HSV-tk gene therapy on hepatic tumor referred as "bystander effect" in therapeutic approach has not been found in this study and required to be explored further.
authors.affiliation: Department of Cell Biology, Capital University of Medical Sciences, Beijing, China.
authors.lastname: Gao Ding Cheng
authors.forename: W
authors.initials: W
authors.lastname: An
authors.forename: J
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D016923:Cell Death; D015774:Ganciclovir / Q000008:administration & dosage*; D015870:Gene Expression; D015316:Genetic Therapy; D006570:Heterochromatin / Q000648:ultrastructure; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008854:Microscopy, Electron; D012190:Retroviridae / Q000235:genetics* / Q000648:ultrastructure; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D006570:Heterochromatin; D013937:Thymidine Kinase; D015774:Ganciclovir