Therapeutic potency of transduction with herpes simplex virus thymidine kinase gene against multidrug resistant mouse leukemia cells.
In order to examine the therapeutic potency of ganciclovir (GCV) against multidrug resistant tumour cells by transduction with the herpes simplex virus thymidine kinase (HSV-TK) gene, vincristine (VCR)-resistant mouse leukemia P388 cells (P388/VCR) were transduced retrovirally with the HSV-TK gene. In vitro, P388/VCR cells expressing HSV-TK (P388/VCR/TK) were approximately 200-fold more sensitive to GCV than P388/VCR cells. Age-matched CDF1 mice were intraperitoneally inoculated with P388/VCR or P388/VCR/TK cells and were treated with either GCV or VCR. The results showed that VCR had little therapeutic effect against P388/VCR/TK-bearing mice, whereas GCV significantly increased the life span of the mice. These results imply the potential value of HSV-TK gene transduction followed by GCV treatment in killing multidrug-resistant tumor cells.
Takenaga
K
K
Division of Chemotherapy, Chiba Cancer Center Research Institute, Japan.
Tagawa
M
M
Sakiyama
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000627:therapeutic use; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015774:Ganciclovir / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D007941:Leukemia P388 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection; D014750:Vincristine / Q000627:therapeutic use
D000970:Antineoplastic Agents; D014750:Vincristine; D004317:Doxorubicin; D013937:Thymidine Kinase; D015774:Ganciclovir