EXPOSURE TO SORBITOL INDUCES RESISTANCE TO CISPLATIN IN HUMAN NON-SMALL-CELL LUNG-CANCER CELL FINES

Cisplatin is the most active anticancer agent for lung cancer. It has been reported that intracellular accumulation of cisplatin is importan t in determining resistance to cisplatin which may be modulated by Na, K+-ATPase activity. On the other hand it is well-known that sorbitol , a metabolite of glucose mediated by aldose reductase, reduces Na+, K +-ATPase in diabetic neuropathy. In this study, the effect of erogenou s sorbitol on Na+, K+-ATPase activity and sensitivity to cisplatin was evaluated using human non-small-cell lung cancer (NSCLC) cell lines. lit the NSCLC cell lines, EBC-1, PC-3, and RERF-LC-MS the cytotoxiciti es of cisplatin were impaired by exposure to sorbitol in these cell li nes. Na+, K+-ATPase was inactivated and intracellular accumulation of cisplatin was decreased by the exposure. These results suggest that ac cumulation of sorbitol may induce resistance to cisplatin in NSCLC cel ls, and diabetes poorly controlled may be one of the determinants of t he antitumor effect of cisplatin in NSCLC.