长春碱在肌苷霉素处理的多药耐药KB细胞中的长期积累。
Long-lasting accumulation of vinblastine in inostamycin-treated multidrug-resistant KB cells.
作者信息
Kawada M, Umezawa K
机构信息
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama.
出版信息
Jpn J Cancer Res. 1991 Oct;82(10):1160-4. doi: 10.1111/j.1349-7006.1991.tb01771.x.
Inostamycin, a novel polyether compound, reverses multidrug resistance in KB cells. The mechanism of its action was studied by use of radioactively labeled vinblastine. Inostamycin dose-dependently increased the accumulation of [3H]vinblastine in multidrug-resistant KB-C4 cells at 0.5-2 micrograms/ml, while it did not enhance accumulation in the drug-sensitive KB-3-1 cells. At a concentration of 1 microgram/ml inostamycin inhibited active [3H]vinblastine efflux from KB-C4 cells, but not from KB-3-1 cells, and inhibited [3H]vinblastine binding to KB-C4 membranes with an IC50 of 0.94 microgram/ml (1.3 microM). Furthermore, [3H]vinblastine accumulated by treatment with 1 microgram/ml of inostamycin was resistant to efflux from KB-C4 cells, even after the removal of inostamycin.
伊诺霉素是一种新型聚醚化合物，可逆转KB细胞的多药耐药性。利用放射性标记的长春碱研究了其作用机制。伊诺霉素在0.5 - 2微克/毫升剂量依赖性地增加了多药耐药KB - C4细胞中[3H]长春碱的积累，而在药物敏感的KB - 3 - 1细胞中未增强积累。在1微克/毫升的浓度下，伊诺霉素抑制了KB - C4细胞中活性[3H]长春碱的流出，但未抑制KB - 3 - 1细胞的流出，并以0.94微克/毫升（1.3微摩尔）的IC50抑制[3H]长春碱与KB - C4细胞膜的结合。此外，用1微克/毫升伊诺霉素处理积累的[3H]长春碱即使在去除伊诺霉素后也对KB - C4细胞的流出具有抗性。
Zotero 插件