Zhang Yu, Yu Jing-Jing, Tian Yan, Li Zheng-Zheng, Zhang Cai-Yi, Zhang Shu-Fen, Cao Lan-Qin, Zhang Yi, Qian Chen-Yue, Zhang Wei, Zhou Hong-Hao, Yin Ji-Ye, Liu Zhao-Qian
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.
Department of Obstetrics & Gynecology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.
Oncotarget. 2015 Sep 22;6(28):25441-51. doi: 10.18632/oncotarget.4555.
The eukaryotic translation initiation factor 3a (eIF3a) is one of the core subunits of the translation initiation complex eIF3, responsible for ribosomal subunit joining and mRNA recruitment to the ribosome. Our previous study identified that it was correlated with platinum response in lung cancer. The current study aims to test the hypothesis that eIF3a may affect the drug response and prognosis of ovarian cancer patients receiving platinum-based chemotherapy by regulating xeroderma pigmentosum complementation group C (XPC) and p27(Kip1). Immunohistochemistry and western blot was used to determine the expression of eIF3a in 126 human ovarian cancer tissues followed by association analysis of eIF3a expression with patient's response and survival. Ectopic over-expression and RNA interference knockdown of eIF3a were carried out in A2780/cisplatin (DDP) and its parental A2780 cells, respectively, to determine the effect of altered eIF3a expression on cellular response to cisplatin by employing MTT assay. Western Blot analyses were also carried out to determine the regulation of eIF3a on XPC and p27(Kip1). eIF3a expression was associated with response of ovarian cancer patients to DDP-based chemotherapy and their survival. Overexpression and knockdown of eIF3a increased and decreased the cellular response to cisplatin in A2780/DDP and A2780 cells, respectively. In addition, XPC and p27(Kip1) were down regulated by eIF3a. eIF3a improves ovarian cancer patients' response to DDP-based chemotherapy via down regulating XPC and p27(Kip1).
真核生物翻译起始因子3a（eIF3a）是翻译起始复合物eIF3的核心亚基之一，负责核糖体亚基的结合以及mRNA募集到核糖体上。我们之前的研究发现它与肺癌的铂类反应相关。当前研究旨在验证以下假设：eIF3a可能通过调节着色性干皮病互补组C（XPC）和p27（Kip1）来影响接受铂类化疗的卵巢癌患者的药物反应和预后。采用免疫组织化学和蛋白质印迹法检测126例人卵巢癌组织中eIF3a的表达，随后对eIF3a表达与患者反应及生存情况进行关联分析。分别在A2780/顺铂（DDP）及其亲本A2780细胞中进行eIF3a的异位过表达和RNA干扰敲低，通过MTT法确定eIF3a表达改变对细胞对顺铂反应的影响。还进行了蛋白质印迹分析以确定eIF3a对XPC和p27（Kip1）的调控作用。eIF3a表达与卵巢癌患者对基于DDP的化疗的反应及其生存情况相关。eIF3a的过表达和敲低分别增加和降低了A2780/DDP和A2780细胞对顺铂的细胞反应。此外，XPC和p27（Kip1）受eIF3a下调。eIF3a通过下调XPC和p27（Kip1）改善卵巢癌患者对基于DDP的化疗的反应。
