EFFECTS OF TAXOTERE ON MURINE AND HUMAN TUMOR-CELL LINES
EFFECTS OF TAXOTERE ON MURINE AND HUMAN TUMOR-CELL LINES
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DOI：
10.1016/s0006-291x(05)81474-3
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发表时间：
1992-08-31
影响因子：
3.1
通讯作者：
LAVELLE, F
中科院分区：
文献类型：
--
作者：
RIOU, JF;NAUDIN, A;LAVELLE, F
泰索帝（RP 56976，NSC 628503）是紫杉醇的类似物，是微管解聚的抑制剂，目前正处于I期临床试验。已在几种鼠（P388、SVras）和人细胞系（Calc 18、HCT 116、T24、N417、KB）中研究了泰索帝和紫杉醇的细胞毒性比较。发现泰索帝比紫杉醇更有效（1.3-12倍），这一结果可以通过其比紫杉醇对微管更高的亲和力来解释。与其假定的作用机制一致，泰索帝对增殖N417细胞的细胞毒性大于对非增殖N417细胞的细胞毒性，并且不抑制细胞DNA、RNA和蛋白质合成。泰索帝对P-糖蛋白耐药的P388/DOX细胞系产生部分交叉耐药，而紫杉醇则产生完全交叉耐药。另一方面，在分别具有拓扑异构酶II和拓扑异构酶I修饰活性的Calc 18/AM和P388/CPT 5细胞系上未观察到交叉耐药。这些结果强调了泰索帝比紫杉醇具有更高的细胞毒活性，并且该类药物与拓扑异构酶I和II相关的多药耐药表型缺乏交叉耐药性。
Taxotere (RP 56976, NSC 628503), an analog of taxol, is an inhibitor of depolymerisation of microtubules and is currently in Phase I clinical trials. Comparisons of the cytotoxicities of Taxotere and taxol have been studied on several murine (P388, SVras) and human cell lines (Calc18, HCT116, T24, N417, KB). Taxotere was found more potent than taxol (1.3–12 fold), a result which could be explained by its higher affinity than taxol for microtubules. In agreement with its postulated mechanism of action, Taxotere is more cytotoxic on proliferating than on non proliferating N417 cells and does not inhibit cellular DNA, RNA and protein synthesis. Taxotere gives partial cross resistance on P-glycoprotein resistant P388/DOX cell line, in contrast to taxol which gives a complete cross resistance. On the other hand, no cross resistances were observed on Calc18/AM and P388/CPT5 cell lines, bearing modified activities of topoisomerase II and topoisomerase I, respectively. These results underline the higher cytotoxic activity of Taxotere compared to taxol, and the lack of cross resistance of that class of agent with the topoisomerase I and II-related multidrug resistance phenotypes.