The Effect of Hyperthermia on p-Glycoprotein Expression, Glutathione Content and Glutathione-related Enzyme Activities in Human Renal Cell Carcinoma Cells.
- Author:
Yeong Cheol HEO
1
;
Eun Sik LEE
;
Won Hee PARK
Author Information
1. Department of Urology, Inha University College of Medicine, Sungnam, Korea.
- Publication Type:Original Article
- Keywords:
Renal cell carcinoma;
Hyperthermia;
Chemotherapeutic agent;
p-Glycoprotein
- MeSH:
Carcinoma, Renal Cell*;
Cell Line;
Cisplatin;
Doxorubicin;
Drug Therapy;
Fever*;
Glutathione Peroxidase;
Glutathione Transferase;
Glutathione*;
Humans*;
P-Glycoprotein*;
Transferases
- From:Korean Journal of Urology
1999;40(2):168-174
- CountryRepublic of Korea
- Language:Korean
-
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.
