Selective beta2-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 non-small cell lung cancer (NSCLC) cell lines. In this study, the effects of the selective beta1, beta2, and beta3-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 beta2-adrenoceptor agonist. Na+, K+-ATPase was activated and intracellular accumulation of cisplatin increased with the treatment. However, beta1 or beta3-adrenoceptor agonist did not modulate sensitivity to cisplatin or Na+, K+-ATPase activity. These results suggest that beta2-adrenoceptor may be one of the determinants for sensitivity to cisplatin in NSCLC. Exogenous beta2-adrenoceptor agonists may improve the antitumor effect of chemotherapy involving cisplatin.
Bando
T
T
Department of Respiratory Medicine, Asanogawa General Hospital, Kanazawa 920-8621, Japan.
Fujimura
M
M
Kasahara
K
K
Ueno
T
T
Matsuda
T
T
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002396:Catechols / Q000494:pharmacology; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004357:Drug Synergism; D004983:Ethanolamines / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011188:Potassium / Q000378:metabolism; D017265:Procaterol / Q000494:pharmacology*; D012694:Serine / Q000031:analogs & derivatives / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000970:Antineoplastic Agents; D002396:Catechols; D004983:Ethanolamines; C076952:SM 11044; D012694:Serine; D000254:Sodium-Potassium-Exchanging ATPase; D002945:Cisplatin; D011188:Potassium; C037293:denopamine; D017265:Procaterol