Selective β2-adrenoceptor agonist enhances sensitivity to cisplatin in non-small cell lung cancer cell line

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 isoproterenol, a beta-adrenoceptor agonist, enhances sensitivity to cisplatin in nonsmall cell lung cancer (NSCLC) cell lines. In this study, the effects of the selective beta 1, beta 2, and beta 3-adrenoceptor agonists on membrane Na+, K+-ATPase activity and sensitivity to cisplatin were evaluated using human non-small cell lung cancer cell line. In the NSCLC cell line, sensitivity to cisplatin was improved by treatment with procaterol, a selective beta 2-adrenoceptor agonist. Na+, K+-ATPase was activated and intracellular accumulation of cisplatin increased with the treatment. However, beta 1 or beta 3-adrenoceptor agonist did not modulate sensitivity to cisplatin or Na+, K+-ATPase activity. These results suggest that beta 2-adrenoceptor may be one of the determinants for sensitivity to cisplatin in NSCLC. Exogenous beta 2-adrenoceptor agonists may improve the antitumor effect of chemotherapy involving cisplatin.