EphA2 affects the sensitivity of oxaliplatin by inducing EMT in oxaliplatin-resistant gastric cancer cells

// Qiaocheng Wen 1 , Zihua Chen 1 , Zhikang Chen 1 , Jinxiang Chen 1 , Ran Wang 1 , Changhao Huang 1 and Weijie Yuan 1 1 General Surgery, Xiangya Hospital, Central South University, Changsha, China Correspondence to: Weijie Yuan, email: ywj0927@126.com Keywords: EphA2, gastric cancer, epithelial–mesenchymal transition, oxaliplatin, drug resistance Received: November 01, 2016     Accepted: April 28, 2017     Published: May 24, 2017 ABSTRACT Erythropoietin-producing hepatocellular receptor A2 (EphA2) is upregulated in gastric cancer tissues and cells, which is accompanied by epithelial–mesenchymal transition (EMT). The current study was designed to establish the oxaliplatin-resistant human gastric cancer cell line SGC-7901/L-OHP, to determine if EMT in these cells could be reversed, and to determine if the susceptibility of these cells to oxaliplatin was affected by silencing EphA2 expression. We found that EphA2 expression levels were upregulated in gastric cancer and associated with chemotherapy sensitivity. EphA2 and the EMT molecular markers N-cadherin and Snail were upregulated in SGC-7901/L-OHP cells, while silencing of EphA2 using small interfering RNA had the opposite effect. Moreover, silencing of EphA2 inhibited cell migration and invasion, and significantly enhanced the sensitivity of oxaliplatin-resistant gastric cancer cells to oxaliplatin. These observations demonstrate that EphA2 affects the sensitivity to oxaliplatin by inducing EMT in oxaliplatin-resistant gastric cancer cells.