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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 related signaling pathways and molecular mechanisms by which COX-2 regulates E-cadherin expression and to reveal the relationship between COX-2 and invasion and metastasis of gastric cancer. Methods The human gastric cancer cell line SGC-7901 was treated with different concentrations of celecoxib, a selective cyclooxygenase-2 inhibitor, for a period of time. Real-time fluorescent quantitative RT-PCR and Western blot were used to detect the expression of COX-2, NF-κB, Snail and E-cadherin mRNA and protein expression. Results The expression of COX-2, NF-κB, Snail mRNA and protein were significantly decreased with the dose of celecoxib and the prolongation of intervention time (P <0.05). E -cadherin mRNA and protein expression increased (P <0.05), in a dose-and time-dependent manner. Spearman correlation analysis showed that COX-2 was positively correlated with the expression of NF-κB, COX-2 and Snail protein (r = 0.881, P <0.01; r = 0.839, The expression was negatively correlated (r = -0.814, P <0.01). Conclusions COX-2 may regulate the expression of E-cadherin via NF-κB / Snail signaling pathway, which may be involved in the invasion and metastasis of gastric cancer.