Riou J F, Naudin A, Lavelle F
Rhône-Poulenc Rorer, Unité de Cancérologie, Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France.
Biochem Biophys Res Commun. 1992 Aug 31;187(1):164-70. doi: 10.1016/s0006-291x(05)81474-3.
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.
泰索帝（RP 56976，NSC 628503）是紫杉醇的类似物，是一种微管解聚抑制剂，目前正处于I期临床试验阶段。已经在几种鼠类（P388、SVras）和人类细胞系（Calc18、HCT116、T24、N417、KB）上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具效力（1.3至12倍），这一结果可以用其对微管的亲和力高于紫杉醇来解释。与其假定的作用机制一致，泰索帝对增殖的N417细胞的细胞毒性比对非增殖的N417细胞更大，并且不抑制细胞DNA、RNA和蛋白质合成。与紫杉醇产生完全交叉耐药性相反，泰索帝对P-糖蛋白耐药的P388/DOX细胞系产生部分交叉耐药性。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Calc18/AM和P388/CPT5细胞系上未观察到交叉耐药性。这些结果强调了泰索帝与紫杉醇相比具有更高的细胞毒性活性，以及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。
