胃癌组织DIMT1表达水平及其对胃癌细胞增殖和迁移能力的影响机制研究

Research of DIMT1 level in gastric cancer and its mechanism to regulate the proliferation and migration of gastric cancer cells

目的分析胃癌组织二甲基腺苷转移酶1(DIMT1)表达水平及其对胃癌细胞增殖和迁移能力的影响机制。方法采用免疫组化法检测DIMT1在胃癌组织及配对癌旁组织中的表达情况;构建稳定过表达DIMT1的SGC-7901胃癌细胞株,采用5-乙炔基-2′脱氧尿嘧啶核苷(EdU)法检测细胞增殖能力,采用细胞划痕实验检测细胞迁移能力,采用裸鼠皮下成瘤实验观察细胞在裸鼠体内的增殖、迁移能力,采用蛋白印迹法检测蛋白激酶B(AKT)、磷酸化AKT(pAKT)和细胞周期蛋白D1(CyclinD1)表达水平。结果胃癌组织DIMT1表达阳性率高于配对癌旁组织(P<0.05)。稳定过表达DIMT1的SGC-7901细胞体外和裸鼠体内增殖和迁移能力均明显升高。AKT、pAKT和CyclinD1蛋白水平随着DIMT1表达水平升高而增高。结论 DIMT1在胃癌组织中表达水平升高,能够增加胃癌细胞增殖和迁移能力,可能成为胃癌治疗靶点。

Objective To investigate the expression level of dimethyladenosine transferase 1(DIMT1) in gastric cancer,and its mechanism to regulate the proliferation and migration of gastric cancer cells. Methods The expression of DIMT1 in gastric cancer tissues and pericarcinoma histologically normal tissues were determined with immunohistochemistry assay.SGC-7901 cell line with over-expression of DIMT1 was constructed.Of the constructed cell line,the proliferation was determined by 5-ethynyl-2′-deoxyuridine(EdU) assay,the migration was monitored by wound healing assay,and the in vivo proliferation and migration in mice were investigated by using subcutaneous tumor model.The protein levels of protein kinases B(AKT),phospho-AKT(pAKT) and CyclinD1 were tested by Western blotting. Results The positive expression rate of DIMT1 in gastric cancer tissues was significantly higher than pericarcinoma tissues.The proliferation and migration of SGC-7901 cells with over-expression of DIMT1 were significantly increased in vivo and in vitro.The protein levels of AKT,pAKT and CyclinD1 were increased with the over-expression of DIMT1. Conclusion DIMT1 could be significantly high expressed in gastric cancer,which could increase the proliferation and migration ability of gastric cancer cells,and might be a potential therapeutic target for gastric cancer.