Liu Chengli, Huang Hui, Wang Cheng, Kong Yalin, Zhang Hongyi
Department of Hepatobiliary Surgery, Air Force General Hospital of PLA, Beijing 100142, P.R. China.
Department of Hepatobiliary Surgery, 309 Hospital of PLA, Beijing 100091, P.R. China.
Oncol Lett. 2014 Jun;7(6):2165-2169. doi: 10.3892/ol.2014.2011. Epub 2014 Mar 28.
Ephrin (EPH) receptors can be classified into EPHA and EPHB receptors and are important in diverse cellular processes. EPHA4, a member of the EPHA receptors, has been demonstrated to be elevated in various human cancers and involved in the tumor progression. However, the role of EPHA4 in pancreatic cancer cells remains unclear. Therefore, the present study transfected Panc-1 and BxPC-3 cells with small interfering RNA (siRNA) to knockdown the expression of EPHA4. Wound healing and invasion assays were then performed to assess the effect of EPHA4 knockdown on the motility and invasion of pancreatic cancer cells. The results demonstrated that the knockdown of EPHA4 by siRNA inhibits the motility and invasion of pancreatic cancer cells. Furthermore, gelatin zymography assay showed that EPHA4 may regulate the activity of matrix metalloproteinase (MMP)-2. In addition, the knockdown of EPHA4 increased the expression of epithelial (E)-cadherin, as well as decreased the expression of Snail. Overall, these results suggested that EPHA4 may promote the motility and invasion of pancreatic cancer cells via the upregulation of MMP-2 and Snail, as well as the downregulation of E-cadherin. Thus, EPHA4 may act as a useful target for the treatment of pancreatic cancer.
Ephrin（EPH）受体可分为EPHA和EPHB受体，在多种细胞过程中发挥重要作用。EPHA4是EPHA受体家族的一员，已证实在多种人类癌症中表达升高，并参与肿瘤进展。然而，EPHA4在胰腺癌细胞中的作用仍不清楚。因此，本研究用小干扰RNA（siRNA）转染Panc-1和BxPC-3细胞，以敲低EPHA4的表达。随后进行伤口愈合和侵袭实验，以评估敲低EPHA4对胰腺癌细胞迁移和侵袭能力的影响。结果表明，siRNA敲低EPHA4可抑制胰腺癌细胞的迁移和侵袭。此外，明胶酶谱分析表明，EPHA4可能调节基质金属蛋白酶（MMP）-2的活性。另外，敲低EPHA4可增加上皮（E）-钙黏蛋白的表达，并降低Snail的表达。总体而言，这些结果提示，EPHA4可能通过上调MMP-2和Snail以及下调E-钙黏蛋白来促进胰腺癌细胞的迁移和侵袭。因此，EPHA4可能成为治疗胰腺癌的一个有效靶点。
