核仁素和骨形态发生蛋白-2在胃癌细胞上皮间质转化中的作用

摘要

目的 上皮间质转化(EMT)在胃癌的发展中发挥重要作用.核仁素(C23)和骨形态发生蛋白-2(BMP2)均与EMT过程相关.但是,BMP2介导EMT的具体机制还不清楚.本研究拟对C23/BMP2在胃癌细胞EMT中的生物学作用进行研究.方法 利用免疫印迹法研究C23和BMP2受体Ⅱ(BMPR-Ⅱ)在多种胃癌细胞系中的表达模式.采用si-C23 RNA处理胃癌细胞系,检测C23表达被阻断后该胃癌细胞中与EMT相关指标的变化.结果 C23和BMPR-Ⅱ在胃癌细胞系中出现异常表达和诱导性表达.MGC803细胞中的p-ERK1/2、p-Akt、波形蛋白、N-钙黏蛋白的表达被BMP2所诱导,且呈现剂量依赖关系.相比之下,si-C23 RNA转染MGC803细胞后,将会减低BMP2诱导的p-Erk1/2、p-Akt、波形蛋白、N-钙黏蛋白和基质金属蛋白酶-2(MMP-2)的表达.另外,si-C23 RNA转染可以降低MGC803细胞的迁移和侵袭能力.结论 在胃癌细胞系中,C23可以经由上调Erk1/2和Akt信号介导BMP2诱导的EMT进程,这表明核仁素(C23)和BMPR-Ⅱ通路可以作为胃癌治疗的潜在靶点或生物标记而发挥重要作用.%Objective In previous study,the epithelial to mesenchymal transition (EMT) has been identified to beinvolved in gastric cancer progression.Notably,nuclear protein C23 and bone morphogenetic protein-2 (BMP2) have been linked into EMT.However,the specific mechanisms underlying BMP2 pathway-mediated EMT are not still unraveled.The paper investigated the biological role of C23 in BMP2-induced EMT in gastric cancer cells.Methods The study adopted immunohistochemistry and immunoblotting to determine the expression of C23 and BMP2 receptor II (BMPR-II) in various gastric cancer cell lines.Subsequently, gastric cancer cell lines were selected to be treated with si C23 and detected the changes of the EMT related indicators after C23 expression was blocked.Results Both C23 and BMPR-II were aberrantly and constitutively expressed in gastric cancer cell lines.In vitro assay validated the increased expression of p-Erk1/2, p-Akt, vimentin,N-cadherin and MMP-2 in BMP2 stimulated MGC803 cells, which was in a dose dependent manner.By contrast, si-C23 treatment attenuated the BMP2 stimulated expression of p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP-2.Also, the treatment of either si-C23 decreased the ability of migration and invasion of MGC803 cells.Conclusion C23 protein meditates bone morphogenetic protein 2 mediated EMT via up regulating of Erk1/2 and Akt in gastric cancer, which indicated both C23 and BMPR-II pathway could be recommended as prospective targets or biomarkers to antagonize the progression of gastric cancer.