Comparison of antiangiogenic activities using paclitaxel (taxol) and docetaxel (taxotere)
Comparison of antiangiogenic activities using paclitaxel (taxol) and docetaxel (taxotere)
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DOI：
10.1002/ijc.10907
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发表时间：
2003-03-10
影响因子：
6.4
通讯作者：
Dicker, AP
中科院分区：
文献类型：
--
作者：
Grant, DS;Williams, TL;Dicker, AP
肿瘤的生长需要一个合格的血管供应和血管生成已被认为是一个潜在的目标，用于治疗几种癌症。两种临床批准的紫杉烷类药物紫杉醇和多西他赛是新型抗有丝分裂药物，正在临床试验中进行广泛研究。两种紫杉烷类药物对许多实体瘤均有显著的抗肿瘤活性，但对紫杉醇和多西他赛对内皮细胞功能和血管生成过程的影响知之甚少。我们的研究目的是检查和比较这些药物在体外和体内对血管生成过程的影响。这些程序包括：培养的人脐静脉内皮细胞（HUVEC）的增殖、迁移和分化（体外），大鼠主动脉环外植体的毛细血管发芽（离体）和体内HT 1080肿瘤生长。我们的研究结果表明，内皮细胞对这些药物的敏感性是肿瘤细胞的10-100倍。此外，紫杉烷类的比较表明，血管生成主要通过抑制增殖和分化（试管试验）和诱导细胞死亡被两种药物阻断。然而，多西紫杉醇似乎在抑制血管生成方面更有效，其IC 50浓度比紫杉醇低10倍。我们的结论是，这些重要的发现应考虑在临床试验中，肿瘤血管生成的目标。(C)2002 Wiley-Liss，Inc.
Tumor growth requires a competent vascular supply and angiogenesis has been considered as a potential target for the treatment of several cancers. The two clinically approved taxanes, paclitaxel and docetaxel, are novel antimitotic agents that are under extensive investigation in clinical trials. Both taxanes have demonstrated significant activity against many solid tumors, but little is known about the effect of paclitaxel and docetaxel on endothelial cell function and angiogenic processes. The purpose of our study was to examine and compare the effects of these drugs on angiogenic processes in vitro and in vivo. These processes include: proliferation, migration and differentiation of cultured human umbilical vein endothelial cells (HUVEC) (in vitro), capillary sprouting of rat aortic ring explants (ex vivo) and HT1080 tumor growth in vivo. Our results demonstrate that endothelial cells are 10-100-fold more sensitive to these drugs than tumor cells. Additionally, comparison of the taxanes demonstrated that angiogenesis is blocked by both drugs primarily via inhibition of proliferation and differentiation (tube assay) and induction of cell death. Docetaxel, however, appears to be more potent at inhibiting angiogenesis, with an IC50 concentration 10x less than that of paclitaxel. We conclude that these important findings should be taken in account in clinical trials where tumor angiogenesis is being targeted. (C) 2002 Wiley-Liss, Inc.