ZEB1对食管癌细胞侵袭转移的影响及作用机制研究

目的 探讨E盒结合锌指蛋白1（zinc finger E-box-binding protein 1，ZEB1）对食管鳞癌（esophageal squamous cell carcinoma，ESCC）增殖和侵袭转移的影响和机制。 方法 选择人ESCC细胞系EC9706细胞为研究对象，采用ZEB1 shRNA对EC9706细胞进行转染，敲除ZEB1表达；采用CCK8法检测细胞活力；细胞侵袭转移能力通过划痕实验检测；利用实时荧光定量聚合酶链反应（real-time quantitative PCR，RT-qPCR）技术检测转染后细胞ZEB1 mRNA表达水平；ZEB1，细胞外调节蛋白激酶（extracellular regulated protein kinase，ERK）1/2，p-ERK1/2， E-cadherin和N-cadherin蛋白表达水平通过免疫印迹（Western blot，WB）检测。 结果 与对照组相比，敲除ZEB1的EC9706细胞系的细胞活力明显降低，并抑制了ESCC的侵袭转移能力（P＜0.05）。ZEB1表达水平降低减少了ERK1/2激活水平，促进E-cadherin表达，抑制N-cadherin表达（P＜0.05）。 结论 下调ZEB1表达抑制ESCC细胞增殖和侵袭转移能力，其作用机制与ERK1/2激活抑制及调控E-cadherin、N-cadherin相关。

Effect of ZEB1 on invasion and metastasis of esophageal cancer cells and its mechanism

Objective The effects of zinc finger E-box-binding protein 1(ZEB1) on cell proliferation, invasion and metastasis of esophageal squamous cell carcinoma(ESCC) and its mechanism.Methods Human ESCC cell line EC9706 was selected, and the ZEB1 shRNA was used to transfect EC9706 cells to knock out ZEB1 expression. The cell viability was determined by CCK8 assay. The ability of cell invasion and migration was detected by scratch test. The expression of ZEB1 shRNA after transfection was detected by Real-Time Quantitative PCR(RT-qPCR). Western blot(WB) was used to determine the protein expressions of extracellular regulated protein kinase(ERK) 1/2, p-ERK1/2, E-cadherin and N-cadherin.Results As compared with the control group, down-regulated ZEB1 expression inhibited the cell viability of EC9706 cells as well as invasion and metastasis ability of ESCC（P＜0.05）. Decreased ZEB1 expression reduced the ERK1/2 activation, increased the expression of E-cadherin, and inhibited the expression of N-cadherin（P＜0.05）.Conclusion The inhibition effects of down-regulated expression of ZEB1 on the proliferation, invasion and metastasis of ESCC cells might be related to the inhibition of ERK1/2 activation and regulation of E-cadherin and N-cadherin.