Stimulation of beta-adrenoceptor enhances sensitivity to cisplatin in non-small cell lung cancer cell lines.

ABSTRACT

Cisplatin is a key drug in chemotherapy for lung cancer. It has been reported that intracellular accumulation of cisplatin is an important step as a determinant for resistance to cisplatin, which may be modulated by Na+, K+-ATPase activity. And it has been reported that beta-adrenoceptor 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, sensitivity to cisplatin was improved by treatment with isoproterenol. Na+, K+-ATPase was activated and intracellular accumulation of cisplatin increased with the treatment. But the antagonist, propranolol, did not modulate sensitivity to cisplatin or Na+, K+-ATPase activity. These results suggest that beta-adrenoceptors may be one of the determinant for sensitivity to cisplatin in NSCLC, but endogenous catecholamine dose not play a role in the intracellular accumulation of cisplatin in these cell lines. Exogenous beta-adrenoceptor agonists may improve the antitumor effect of chemotherapy involving cisplatin.