Exposure to sorbitol induces resistance to cisplatin in human non-small-cell lung cancer cell lines.

Cisplatin is the most active anticancer agent for lung cancer. It has been reported that intracellular accumulation of cisplatin is important 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 exogenous sorbitol on Na+, K(+)-ATPase activity and sensitivity to cisplatin was evaluated using human non-small-cell lung cancer (NSCLC) cell lines. In the NSCLC cell lines, EBC-1, PC-3, and RERF-LC-MS the cytotoxicities of cisplatin were impaired by exposure to sorbitol in these cell lines. Na+, K(+)-ATPase was inactivated and intracellular accumulation of cisplatin was decreased by the exposure. These results suggest that accumulation of sorbitol may induce resistance to cisplatin in NSCLC cells, and diabetes poorly controlled may be one of the determinants of the antitumor effect of cisplatin in NSCLC.