Retrovirus-mediated herpes simplex virus thymidine kinase gene therapy approach for hepatocellular carcinoma.
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.
Gao Ding Cheng
Department of Cell Biology, Capital University of Medical Sciences, Beijing, China.
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Dai
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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
D006570:Heterochromatin; D013937:Thymidine Kinase; D015774:Ganciclovir