STAUROSPORINE, A POTENT INHIBITOR OF C-KINASE, ENHANCES DRUG ACCUMULATION IN MULTIDRUG-RESISTANT CELLS
STAUROSPORINE, A POTENT INHIBITOR OF C-KINASE, ENHANCES DRUG ACCUMULATION IN MULTIDRUG-RESISTANT CELLS
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DOI：
10.1016/s0006-291x(05)80921-0
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发表时间：
1990-12-31
影响因子：
3.1
通讯作者：
TSURUO, T
中科院分区：
文献类型：
--
作者：
SATO, W;YUSA, K;TSURUO, T
星形孢菌素是一种强效C激酶抑制剂，可增强长春新碱（VCR）在多药耐药细胞中的蓄积。我们通过两种方法研究了这种增强作用：（I）ATP依赖的VCR结合系统;（II）叠氮平光标记系统。星形孢菌素比维拉帕米更有效地抑制ATP依赖性VCR与抗性细胞膜的结合。星形孢菌素也抑制P-糖蛋白的叠氮平光标记。这些结果表明，星形孢菌素，一种C-激酶抑制剂，可能直接结合P-糖蛋白以及抗肿瘤药物和钙通道阻滞剂。这些结果也表明C激酶可能参与P糖蛋白的功能。
Staurosporine, a potent inhibitor of C-kinase, enhances accumulation of vincristine (VCR) in multidrug-resistant cells. We investigated this enhancement by two methods: (I) ATP-dependent VCR binding system; (II) azidopine photolabeling system. The ATP-dependent VCR binding to the resistant cell membrane was inhibited more efficiently by staurosporine than by verapamil. Staurosporine also inhibited the azidopine photolabeling of P-glycoprotein. These results indicate that staurosporine, an inhibitor of C-kinase, might directly bind to P-glycoprotein as well as antitumor agents and Ca2+channel blockers. These findings also indicate that C-kinase might be involved in the function of P-glycoprotein.