The Effect of Hyperthermia on p-Glycoprotein Expression, Glutathione Content and Glutathione-related Enzyme Activities in Human Renal Cell Carcinoma Cells / 대한비뇨기과학회지

ABSTRACT

PURPOSE: Resistance to anticancer chemotherapeutic drug remains a major obstacle in cancer chemotherapy. Multidrug-resistance(MDR) gene overexpression and detoxification by glutathione are believed to be involved in adriamycin and cisplatin resistance. We investigated change of p-glycoprotein(MDR gene product) expression, cellular glutathione content and glutathione peroxidase and glutathione transferase activities by hyperthermia to elucidate the synergistic mechanism of hyperthermia with chemotherapeutic agent. MATERIALS AND METHODS: Human renal cell carcinoma cell lines, Caki-1 and A-498 were used. Control temperature was 37OC and hyperthermia of 43OC was applied in 2 and 4 hours durations. P-glycoprotein expression was measured by flowcytometric examination using monoclonal antibody to p-glycoprotein. Glutathione content and activities of glutathione peroxidase and transferase were measured by biochemical methods. RESULTS: Glutathione content and activities of glutathione peroxidase and transferase were not changed by hyperthermia. However, p-glycoprotein expression was reduced by hyperthermia of 43OC. CONCLUSIONS: These results suggest that reduced p-glycoprotein expression by hyperthermia causes increased intracellular accumulation of chemotherapeutic agent by decreasing drug efflux mechanism and plays an important role in synergistic effect with adriamycin and cisplatin cytotoxicities.