Combined antimicrotubule activity of estramustine and taxol in human prostatic carcinoma cell lines.
Combined antimicrotubule activity of estramustine and taxol in human prostatic carcinoma cell lines.
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发表时间：
1992-08
期刊：
影响因子：
11.2
通讯作者：
L. Speicher;L. Barone;K. Tew
中科院分区：
文献类型：
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作者：
L. Speicher;L. Barone;K. Tew
雌莫司汀（EM）和紫杉醇，两种具有不同的和明显相反的作用机制的抗微管剂，被发现是有效的组合在EM耐药和敏感的，野生型人前列腺癌细胞系的临床前治疗。雌莫司汀与1 nM紫杉醇（浓度比紫杉醇治疗患者血浆中测得的浓度低100倍）组合对野生型和EM耐药细胞的细胞存活抑制产生大于累加效应。当紫杉醇与另一种微管不稳定药物长春碱一起使用时，没有观察到明显增加的细胞毒性。EM和紫杉醇联合给药对野生型和EM耐药细胞的其他影响包括：（a）细胞周期S期细胞比例增加;（B）无有丝分裂阻滞;（c）药物处理后微核细胞百分比从对照值（小于1%）增加至大于20%。这种药物组合对有丝分裂纺锤体装置的影响的免疫荧光显微镜分析揭示了异常有丝分裂图的具体实例，包括多个星形细胞、具有两个不同纺锤体的细胞和能够穿过有丝分裂和完成胞质分裂的三极纺锤体。这些数据为EM/紫杉醇联合治疗前列腺癌或其他癌症的临床方案的潜在开发提供了支持性临床前证据。
Estramustine (EM) and taxol, two antimicrotubule agents with distinct and apparently opposing mechanisms of action, were found to be effective in combination in the preclinical treatment of EM-resistant and sensitive, wild-type human prostatic carcinoma cell lines. Estramustine combined with 1 nM taxol (concentration 100-fold less than that measured in plasma of patients treated with taxol) produced greater than additive effects on the inhibition of cell survival of both wild-type and EM-resistant cells. When taxol was used with another microtubule-destabilizing drug, vinblastine, no significantly increased cytotoxicity was observed. Other effects on wild-type and EM-resistant cells produced by the combination of EM and taxol included (a) an increased proportion of the cells in the S phase of the cell cycle; (b) no mitotic block; and (c) an increase in the percentage of micronucleated cells from a control value of less than 1% to greater than 20% after drug treatment. Immunofluorescent microscopic analysis of the effect of this drug combination on the mitotic spindle apparatus revealed specific examples of aberrant mitotic figures, including multiple asters, cells with two distinct spindles, and tripolar spindles able to traverse mitosis and complete cytokinesis. These data provide supportive preclinical evidence for the potential development of an EM/taxol combination clinical regimen either for prostate or other cancers.