Wen Qiaocheng, Chen Zihua, Chen Zhikang, Chen Jinxiang, Wang Ran, Huang Changhao, Yuan Weijie
General Surgery, Xiangya Hospital, Central South University, Changsha, China.
Oncotarget. 2017 Jul 18;8(29):47998-48011. doi: 10.18632/oncotarget.18208.
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.
促红细胞生成素产生肝细胞受体A2（EphA2）在胃癌组织和细胞中表达上调，同时伴有上皮-间质转化（EMT）。本研究旨在建立耐奥沙利铂的人胃癌细胞系SGC-7901/L-OHP，确定这些细胞中的EMT是否可以逆转，以及沉默EphA2表达是否会影响这些细胞对奥沙利铂的敏感性。我们发现EphA2表达水平在胃癌中上调，并与化疗敏感性相关。EphA2以及EMT分子标志物N-钙黏蛋白和Snail在SGC-7901/L-OHP细胞中上调，而使用小干扰RNA沉默EphA2则产生相反的效果。此外，沉默EphA2抑制细胞迁移和侵袭，并显著增强耐奥沙利铂胃癌细胞对奥沙利铂的敏感性。这些观察结果表明，EphA2通过诱导耐奥沙利铂胃癌细胞中的EMT来影响对奥沙利铂的敏感性。
