Mechanism of action of taxol.
Mechanism of action of taxol.
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DOI：
10.1016/0165-6147(92)90048-b
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发表时间：
1992
影响因子：
13.8
通讯作者：
S. B. Horwitz
中科院分区：
文献类型：
--
作者：
S. B. Horwitz
对有丝分裂中与微管作用并阻断细胞的机制知之甚少。基本上没有关于tax 01与微管结合的位点或tax 01对某些恶性肿瘤显示的特异性的信息。紫杉醇耐药肿瘤细胞已在实验室中分离和分析。两种不同形式的抵抗已经被描述。一系列突变的中国仓鼠卵巢细胞=具有改变的LX-和/或@-微管蛋白亚基，赋予对紫杉醇的抗性;其他细胞已经变得依赖紫杉醇，并且实际上需要药物进行细胞复制。通过聚丙烯酰胺凝胶电泳期间的异常迁移来鉴定改变的微管蛋白亚基。紫杉醇的极端疏水性质和其天然产物来源使其成为诱导多药耐药表型的理想候选物。用紫杉醇从药物敏感的小鼠肿瘤J774中筛选出高度耐药的细胞系。2细胞表现出包括P-糖蛋白2425过量产生的YPe #表型。后者是一种完整的膜糖蛋白，作为能量依赖性药物外排泵，以维持细胞内药物浓度低于细胞毒性水平。人类白血病细胞系对紫杉醇的耐药性与多倍体细胞的形成有关;然而，关于人类肿瘤中可能产生的耐药性类型的信息很少。
acts with miaotubules and blocks cells in mitosis is poorly understood. Essentially there is no information on the site (s) at which tax01 binds to microtubules or on the specificity that tax01 displays toward certain malignant tumors. Taxol-resistant tumor cells have been isolated and analysed in the laboratory. Two distinct forms of resistance have been described. A series of mutant Chinese hamster ovary cells= have altered LX-and/or@-tubulin subunits that confer resistance to taxol; others have become dependent on taxol, and actually require the drug for cell replication. The altered tubulin subunits were identified by aberrant migration during electrophoresis on polyacrylamide gels. Taxol’s extreme hydrophobic nature and its natural product origin make it a perfect candidate for the induction of the multidrug resistance phenotype. A highly resistant cell line selected with taxol from drug-sensitive murine tumor J774. 2 cells displays this phenofYPe# including overproduction of P-glycoprotein2425. The latter is an integral membrane glycoprotein that acts as an energydependent drug efflux pump to maintain intracellular drug concentrations below cytotoxic levels. Resistance to taxol in human leukemia cell lines has been correlated with the development of polyploid cells%; however, there is little information on the types of resistance that may develop in human tumors.