Role of inhibitor of yes-associated protein 1 in triple-negative breast cancer with taxol-based chemoresistance
Role of inhibitor of yes-associated protein 1 in triple-negative breast cancer with taxol-based chemoresistance
复制标题
Yes相关蛋白1抑制剂在基于紫杉醇化疗耐药的三阴性乳腺癌中的作用
DOI：
10.1111/cas.13888
复制
发表时间：
2019-02-01
期刊：
影响因子：
5.7
通讯作者：
Zhang, Jin
中科院分区：
文献类型：
--
作者：
Li, Ying;Wang, Shunan;Zhang, Jin
三阴性乳腺癌（TNBC）在临床上具有高度侵袭性，基于紫杉醇的化疗耐药性仍然是一个有待解决的 TNBC 治疗大问题。维替泊芬是一种小分子 yes 相关蛋白 1 (YAP1) 抑制剂，但作为 TNBC 的抗肿瘤药物却鲜为人知。我们的数据显示，YAP1 表达与 TNBC 紫杉醇化疗耐药患者的组织样本中的早期复发相关 (P < .001)。体外，维替泊芬可减少紫杉醇耐药 MDA-MB-231 细胞系的迁移并增强细胞凋亡或自噬。 YAP1 的敲除增加了紫杉醇耐药 TNBC 细胞系的上皮间质转化反应。在体内实验中，我们发现维替泊芬能够缩小紫杉醇抗性小鼠模型中的肿瘤重量和体积，并降低 Ki67 表达。我们的研究结果证明，维替泊芬可能是接受紫杉醇治疗的 TNBC 患者的化疗增敏剂。
Triple-negative breast cancer (TNBC) is highly clinically aggressive and taxol-based chemoresistance remains a big TNBC therapeutic problem to be solved. Verteporfin, a small molecular yes-associated protein 1 (YAP1) inhibitor, is little known as an antitumor drug for TNBC. Our data showed that YAP1 expression was associated with early relapse in tissue samples of patients with TNBC taxol chemoresistance (P < .001). Verteporfin reduced migration and enhanced apoptosis or autophagy of a taxol-resistant MDA-MB-231 cell line in vitro. Knockdown of YAP1 increased epithelial-mesenchymal transition response in a taxol-resistant TNBC cell line. In an in vivo experiment, we found that verteporfin was able to shrink tumor weight and volume and decreased Ki67 expression in a taxol-resistant mouse model. Our results provide evidence that verteporfin could be a chemosensitizer for TNBC patients with taxol-based treatment.