Korean J Urol.  1999 Feb;40(2):168-174.

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

• Heo YC
• Lee ES
• Park WH

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.

Keyword

Renal cell carcinoma; Hyperthermia; Chemotherapeutic agent; p-Glycoprotein

MeSH Terms

Carcinoma, Renal Cell*
Cell Line
Cisplatin
Doxorubicin
Drug Therapy
Fever*
Glutathione Peroxidase
Glutathione Transferase
Glutathione*
Humans*
P-Glycoprotein*
Transferases
Cisplatin
Doxorubicin
Glutathione
Glutathione Peroxidase
Glutathione Transferase
P-Glycoprotein
Transferases