Selective beta 2-adrenoceptor agonist enhances sensitivity to cisplatin innon-small cell lung cancer cell line

Cisplatin is a key drug in chemotherapy for lung cancer. It has been report ed that intracellular accumulation of cisplatin is an important step as a d eterminant for resistance to cisplatin, which may be modulated by Na+, K+-A TPase activity. And it has been reported that isoproterenol, a beta-adrenoc eptor agonist, enhances sensitivity to cisplatin in nonsmall cell lung canc er (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 activit y and sensitivity to cisplatin were evaluated using human non-small cell lu ng cancer cell line. In the NSCLC cell line, sensitivity to cisplatin was i mproved by treatment with procaterol, a selective beta 2-adrenoceptor agoni st. Na+, K+-ATPase was activated and intracellular accumulation of cisplati n increased with the treatment. However, beta 1 or beta 3-adrenoceptor agon ist did not modulate sensitivity to cisplatin or Na+, K+-ATPase activity. T hese results suggest that beta 2-adrenoceptor may be one of the determinant s for sensitivity to cisplatin in NSCLC. Exogenous beta 2-adrenoceptor agon ists may improve the antitumor effect of chemotherapy involving cisplatin.