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CLIN CANCER RES：顺铂耐药的卵巢癌中存在有丝分裂退出异常

2018-09-30 MedSci MedSci原创

卵巢癌顺铂耐药有丝分裂退出
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顺铂获得性耐药是成功治疗各种癌症的主要障碍。了解顺铂耐药肿瘤细胞特有的有丝分裂机制可为开发靶向有丝分裂的新型疗法提供基础。CLIN CANCER RES近期发表了一篇文章研究这一问题。

顺铂获得性耐药是成功治疗各种癌症的主要障碍。了解顺铂耐药肿瘤细胞特有的有丝分裂机制可为开发靶向有丝分裂的新型疗法提供基础。CLIN CANCER RES近期发表了一篇文章研究这一问题。

作者使用原发性上皮性卵巢癌（EOC）患者来源的肿瘤细胞建立顺铂耐药模型，研究顺铂耐药细胞中有丝分裂退出的机制。研究结果表明，长期顺铂治疗在诱导有丝分裂退出易感性中起到了意想不到的作用，其特征是纺锤体检查点活性增加以及在顺铂耐药状态下的 APC / C功能障碍。在体内和体外实验中，PLK1阻滞降低了顺铂耐药细胞的存活，并且在这些细胞中增强了纺锤体检查点反应。APC / C CDC20阻滞增加了对PLK1抑制的敏感性，进一步证实顺铂耐药细胞中存在APC / C功能障碍。此外，作者还发现volasertib（PLK1抑制剂）耐药是由于细胞持续低表达PLK1。顺铂耐药细胞中持续的PLK1下调诱导volasertib耐药。

文章最后认为，该研究为顺铂耐药状态下APC / C功能障碍提供了证据，理解顺铂耐药状态下的APC / C功能可为开发新的疗法提供基础，以根除顺铂耐药癌细胞。研究结果还表明，PLK1下调可能是肿瘤PLK1靶向治疗的耐药性基础。

原始出处：

Anil Belur Nagaraj, Olga Kovalenko,et al. Mitotic Exit Dysfunction through the Deregulation of APC/C Characterizes Cisplatin-Resistant State in Epithelial Ovarian Cancer.CLIN CANCER RES.September 2018 doi: 10.1158/1078-0432.CCR-17-2885

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    2019-02-04 yeye5224612

    #顺铂耐药#

    0

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    2018-12-31 ms3153534357578991

    #铂#

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    2019-03-31 lujian

    #有丝分裂退出#

    0

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    2018-10-02 tamgche

    #有丝分裂#

    0

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