Inhibition of Hec1 expression enhances the sensitivity of human ovarian cancer cells to paclitaxel
Inhibition of Hec1 expression enhances the sensitivity of human ovarian cancer cells to paclitaxel
复制标题
抑制Hec1表达增强人卵巢癌细胞对紫杉醇的敏感性
DOI：
10.1038/aps.2012.197
复制
发表时间：
2013-04-01
影响因子：
8.2
通讯作者：
Chen, Gang
中科院分区：
文献类型：
--
作者：
Mo, Qing-qing;Chen, Ping-bo;Chen, Gang
目的：Hec 1是Ndc 80动粒复合体的成员，在肿瘤中高度表达。本研究旨在探讨Hec 1在紫杉醇杀伤卵巢癌细胞中的作用及其机制。用免疫组织化学方法检测这些样本中Hec 1的表达。检查卵巢癌细胞系A2780、OV 2008、C13 K、SKOV 3和CAOV 3以及A2780/Taxol。流式细胞术检测细胞凋亡和细胞周期。siRNA用于删除细胞中的Hec 1。结果：Hec 1在卵巢癌组织中的表达明显高于正常卵巢组织，且与卵巢癌患者的紫杉醇耐药及预后不良有关。在检测的6种卵巢癌细胞系中，Hec 1在紫杉醇耐药的A2780/Taxol细胞中表达最高，在A2780细胞中表达最低。在A2780/Taxol细胞中用siRNA耗尽Hec 1使紫杉醇的IC 50值降低了10倍以上（从590 +/- 26.7到45.6 +/- 19.4 nmol/L）。在A2780细胞中耗尽Hec 1对紫杉醇敏感性没有显著影响。在紫杉醇处理的A2780/Taxol细胞中，去除Hec 1可显著增加PARP和Bax蛋白水平，降低Bcl-xL蛋白水平。结论：Hec 1过表达与卵巢癌的进展和不良预后有关。抑制Hec 1表达可使卵巢癌细胞对紫杉醇敏感。
Aim: Hec1, a member of the Ndc80 kinetochore complex, is highly expressed in cancers. The aim of this study was to explore the role and mechanism of action of Hec1 with respect to the cytotoxicity of paclitaxel in ovarian cancer.Methods: Thirty ovarian cancer samples and 6 normal ovarian samples were collected. Hec1 expression in these samples was determined with immunohistochemistry. Ovarian cancer cell lines A2780, OV2008, C13K, SKOV3, and CAOV3 and A2780/Taxol were examined. Cell apoptosis and cell cycle analysis were detected with flow cytometric technique. siRNA was used to delete Hec1 in the cells. The expression of related mRNAs and proteins was measured using RT-PCR and Western blot analysis, respectively.Results: Hec1 expression was significantly higher in ovarian cancer samples than in normal ovarian samples, and was associated with paclitaxel-resistance and poor prognosis. Among the 6 ovarian cancer cell lines examined, Hec1 expression was highest in paclitaxel-resistant A2780/Taxol cells, and lowest in A2780 cells. Depleting Hec1 in A2780/Taxol cells with siRNA decreased the IC50 value of paclitaxel by more than 10-fold (from 590 +/- 26.7 to 45.6 +/- 19.4 nmol/L). Depleting Hec1 in A2780 cells had no significant effect on the paclitaxel sensitivity. In paclitaxel-treated A2780/Taxol cells, depleting Hec1 significantly increased the cleaved PARP and Bax protein levels, and decreased the Bcl-xL protein level.Conclusion: Hec1 overexpression is associated with the progression and poor prognosis of ovarian cancer. Inhibition of Hec1 expression can sensitize ovarian cancer cells to paclitaxel.