eIF3a improve cisplatin sensitivity in ovarian cancer by regulating XPC and p27Kip1 translation

// Yu Zhang 1, 3 , Jing-Jing Yu 3 , Yan Tian 3 , Zheng-Zheng Li 3 , Cai-Yi Zhang 3 , Shu-Fen Zhang 3 , Lan-Qin Cao 3 , Yi Zhang 3 , Chen-Yue Qian 1, 2 , Wei Zhang 1, 2 , Hong-Hao Zhou 1, 2 , Ji-Ye Yin 1, 2 , Zhao-Qian Liu 1, 2 1 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China 2 Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China 3 Department of Obstetrics & Gynecology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China Correspondence to: Zhao-Qian Liu, e-mail: liuzhaoqian63@126.com Ji-Ye Yin, e-mail: yinjiye@csu.edu.cn Keywords: eIF3a, platinum, ovarian cancer, drug resistance, XPC Received: April 30, 2015 Accepted: June 29, 2015 Published: July 11, 2015 ABSTRACT 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 .