环氧合酶2通过上皮间质转换促进胃癌的侵袭与转移

Cyclooxygenase-2 promotes gastric cancer invasion and metastasis by inducing epithelial to mesenchymal transition

目的:探讨环氧合酶2(COX-2)及Snail在胃癌组织中的表达及临床意义,研究COX-2转染对人胃癌细胞侵袭迁移能力的影响并探讨其机制。方法:免疫组化检测COX-2及Snail在100例胃癌组织中的表达情况,分析其与临床资料的关系;筛选构建COX-2稳定表达的MKN74、MKN45细胞系;观察转染前后细胞的形态、功能及相关蛋白的改变。结果:COX-2的表达与远处转移、淋巴结转移、不良预后密切相关(P<0.05);Snail的表达与分期、淋巴结转移、远处转移相关(P<0.05);COX-2的表达与Snail之间存在相关性(P<0.01)。与对照组相比,MKN74/COX-2细胞形态呈现EMT形态学改变,E-cadherin表达下调、Vimentin表达上调,迁移侵袭能力明显增强;MKN45/sh COX-2细胞形态由长梭形变为铺路石样,E-cadherin表达上调、Vimentin表达下调,迁移侵袭能力减弱。结论:COX-2可以通过EMT促进胃癌细胞的侵袭和转移。

Objective： To determine the expressions of Cyclooxygenase-2（COX-2） and Snail in gastric cancer, investigate the effect of COX-2 transduction on invasion and migration of gastric cancer cell lines of MKN74 and MKN45, and explore its related mechanism.Methods： The expressions of COX-2 and Snail were examined by immunohistochemical technique. Lentiviruses carrying COX-2 gene were constructed and transducted into MKN74 and MKN45. The changes in morphology, migration, invasion and protein were detected.Results： The expression of COX-2 was positively correlated with metastasis in lymph node and metastasis in distance（P〈0.05）. Snail expression was related to stage, lymph node metastasis and distant metastasis in human gastric cancer（P〈0.05）.There was a positive correlation between COX-2 and Snail expressions（P〈0.01）. The MKN74/COX-2 cells showed EMT changes. The migration and invasion abilities were significantly enhanced. Knockdown of COX-2 resulted in inhibited EMT in MKN45 cells. Migration and invasion abilities were significantly receded in MKN45/sh COX-2 cells. Conclusion： COX-2 plays an important role in the origin and development of gastric cancer, COX-2 through EMT promotes the migration and invasion abilities in gastric cancer cells.