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Therapeutic potency of transduction with herpes simplex virus thymidine kinase gene against multidrug resistant mouse
K Takenaga1, M Tagawa, S Sakiyama
1Division of Chemotherapy, Chiba Cancer Center Research Institute, Japan.
Abstract:
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.