Title | Retrovirus-mediated herpes simplex virus thymidine kinase gene therapy approach for hepatocellular carcinoma. |
Publication Type | Journal Article |
Year of Publication | 1999 |
Authors | An W, Dai J |
Journal | Cell Res |
Volume | 9 |
Issue | 3 |
Pagination | 225-35 |
Date Published | 1999 Sep |
ISSN | 1001-0602 |
Keywords | Animals, Blotting, Southern, Carcinoma, Hepatocellular, Cell Death, Ganciclovir, Gene Expression, Genetic Therapy, Heterochromatin, Humans, Liver Neoplasms, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Microscopy, Electron, Retroviridae, Simplexvirus, Thymidine Kinase, Transfection, Tumor Cells, Cultured |
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. |
DOI | 10.1038/sj.cr.7290021 |
Alternate Journal | Cell Res |
PubMed ID | 10520605 |