胃癌细胞中COX-2通过NF-κB/Snail调控E-cadherin表达的机制

COX-2 regulates expression of E-cadherin in human gastric carcinoma cells through NF-κB/Snail pathway

目的探讨COX-2调控E-cadherin表达的相关信号通路及分子机制,揭示COX-2与胃癌侵袭转移的关系及作用机制。方法采用不同浓度的选择性COX-2抑制剂塞来昔布干预人胃癌细胞株SGC-7901不同时间后,应用实时荧光定量RT-PCR法和Western blot法检测SGC-7901细胞中COX-2、NF-κB、Snail及E-cadherin mRNA和蛋白的表达情况。结果随着塞来昔布作用剂量的增大和干预时间的延长,COX-2、NF-κB和Snail mRNA及蛋白的表达量均显著下降(P<0.05),呈剂量和时间依赖性降低;E-cadherin mRNA及蛋白的表达量上升(P<0.05),呈剂量和时间依赖性升高。采用Spearman相关分析,显示COX-2与NF-κB及COX-2与Snail蛋白表达呈正相关性(r=0.881,P<0.01;r=0.839,P<0.01);COX-2与E-cadherin蛋白表达呈负相关性(r=-0.814,P<0.01)。结论COX-2可能通过NF-κB/Snail信号通路调控E-cadherin的表达,进而参与胃癌的浸润转移过程。

Objective To investigate the mechanisms related to the expression of E-cadherin regulated by COX-2 in human gastric cancer cells. Methods Human gastric cancer SGC-7901 cells were treated with eyclooxygenase-2 （COX-2） inhibitor, celecoxib, at different concentrations for different durations. Western blot and real time quantitative RT-PCR were used to detect mRNA and protein expression of COX-2,NF-κB,Snail and E-cadherin. Results The mRNA and protein expressions of COX-2 ,NF-κB and Snail in SGC-7901 cells declined and those of E-eadherin increased significantly after treated with celecoxib （ P 〈 0.05 ） , in a dose- and time-dependent manner. The expression of COX-2 was positively correlated with NF-κB （ r = 0.881 ,P 〈 0.01 ） and Snail （ r = 0.839 ,P 〈 0. 01 ） level, and was negatively correlated with E- cadherin level （r = - 0. 814,P 〈 0.01 ）. Conclusion COX-2 may regulate the expression of E-cadherin through NF-κB and Snail signaling pathway during gastric cancer progression.