塞来昔布干预对人胃癌细胞E-钙黏蛋白和基质金属蛋白酶-2表达的影响

The effect of celecoxib on the expression of E-cadherin and MMP-2 in human gastric carcinoma cell line SGC7901 in vitro

目的探讨COX-2与E-cadherin、MMP-2之间的相互关系及其参与胃癌细胞侵袭迁移的可能机制。方法应用塞来昔布(celecoxib)对体外培养的人胃癌细胞SGC7901进行干预,采用实时荧光定量反转录PCR检测COX-2、E-cadherin、MMP-2 mRNA的表达;运用免疫荧光标记法结合激光共聚焦荧光显微镜分析E-cadherin的蛋白表达量;应用Transwell法检测细胞侵袭及迁移能力的变化。结果塞来昔布明显抑制体外培养的人胃癌细胞SGC-7901中COX-2 mRNA的表达,E-cadherin mRNA的表达随着COX-2的表达下降而呈浓度与时间依赖性升高,MMP-2 mRNA的表达随着COX-2的表达下降而呈浓度与时间依赖性降低。塞来昔布30μmol/L干预人胃癌细胞SGC7901 24、36、48 h后,激光共聚焦荧光显微镜检测E-cadherin的蛋白表达量明显升高。塞来昔布干预组细胞穿过Transwell小室的细胞数明显少于对照组。结论 COX-2特异性抑制剂塞来昔布通过抑制COX-2的表达,上调E-cadherin的表达,下调MMP-2的表达,抑制体外培养的胃癌细胞SGC7901的侵袭迁移能力。

Objective To explore the relationship of the expression of COX-2 and E-cadherin, MMP-2, and the mechanism of COX-2 involvement in the tumor cell invasion and migration. Methods Celecoxib had been used to inter- vene in the gastric carcinoma cell line SGC7901, the real-time quantitative PCR was used to detect the levels of COX-2, E-cadherin and MMP-2 mRNA. The combination immunofluorescence and confocal laser scanning microscopy was used to analyze the expression of E-cadherin protein. Transwell was used to detect the effect of celecoxib on the invasion and migration of human gastric carcinoma cells. Results Celecoxib significantly inhibited the expression of COX-2 mRNA, with a corresponding E-cadherin mRNA expression gradually increased and MMP-2 mRNA expression gradually de- creased. Application of celecoxib （30 μmol/L） treatment in human gastric cancer cell SGC-7901, the confocal laser fluorescence microscope scanning detected that the expression of E-cadherin protein at 24, 36, 48 hours significantly in- creased. The number of cells in celecoxib treated group through the Transwell chamber was less than the number of cells in the control group. Conclusion Selective COX-2 inhibitor eeleeoxib may up-regulate the expression of E-cadherin, and clown-regulate the expression of MMP-2, which can inhibite the invasion and migration of human gastric carcinoma by suppressing the expression of COX-2 in vitro.