STIMULATION OF BETA-ADRENOCEPTOR ENHANCES SENSITIVITY TO CISPLATIN INNONSMALL CELL LUNG-CANCER CELL-LINES

Cisplatin is a key drug in chemotherapy for lung cancer. It has been r eported that intracellular accumulation of cisplatin is an important s tep as a determinant for resistance to cisplatin, which may be modulat ed by Na+, K+-ATPase activity. And it has been reported that beta-adre noceptor agonists modulate the Na+, K+-ATPase in some organs. In this study, the effects of a beta-adrenoceptor agonist and an antagonist on membrane Na+, K+-ATPase activity were evaluated using human non-small cell (NSCLC) lung cancer cell lines. In the NSCLC cell lines, sensiti vity to cisplatin was improved by treatment with isoproterenol. Na+, K +-ATPase was activated and intracellular accumulation of cisplatin inc reased with the treatment. But the antagonist, propranolol, did not mo dulate sensitivity to cisplatin or Na+, K+-ATPase activity. These resu lts suggest that beta-adrenoceptors may be one of the determinant for sensitivity to cisplatin in NSCLC, but endogenous catecholamine dose n ot play a role in the intracellular accumulation of cisplatin in these cell lines. Exogenous beta-adrenoceptor agonists may improve the anti tumor effect of chemotherapy involving cisplatin.