MicroRNA-21通过PTEN/Akt通路介导前列腺素E_2促进胃癌细胞的增殖  

MicroRNA-21 Mediates the Promoting of Proliferation of Gastric Cancer Cells by Prostaglandin E_2 through PTEN/Akt Pathway

作　　者：周皓[1] 张绍仁[1] 刘红燕[1] 

机构地区：[1]复旦大学附属金山医院消化内科,201508

出　　处：《胃肠病学》2016年第8期474-478,共5页Chinese Journal of Gastroenterology

基　　金：复旦大学附属金山医院院级课题(2013-院743)

摘　　要：背景:已有研究证实前列腺素E_2(PGE_2)可促进肿瘤细胞的增殖,microRNA-21(miR-21)可抑制肿瘤细胞增殖,但信号通路尚不明确。目的:探讨miR-21介导PGE_2促进胃癌细胞增殖的潜在作用机制。方法:体外培养胃癌AGS细胞,分为对照组、PGE_2组、anti-miR-21组、PGE_2+anti-miR-21组,以WST-1比色法检测细胞生存率,流式细胞术检测细胞凋亡率,RT-PCR法检测miR-21 mRNA表达。以Akt特异性抑制剂哌立福辛干预AGS细胞,检测其对细胞增殖的影响,蛋白质印迹法检测PTEN/Akt蛋白表达。结果:与对照组相比,PGE_2组AGS细胞生存率显著升高(P<0.05),凋亡率显著降低(P<0.05),miR-21 mRNA表达显著升高(P<0.05)。与PGE_2组相比,anti-miR-21组、PGE_2+anti-miR-21组细胞生存率显著降低(P<0.05),凋亡率显著升高(P<0.05),miR-21 mRNA表达显著降低(P<0.05)。以哌立福辛干预后,AGS细胞生存率显著降低(P<0.05),凋亡率显著升高(P<0.05),PTEN蛋白表达明显上调,p-Akt蛋白表达明显下调。结论:miR-21通过PTEN/Akt通路介导了PGE_2促进胃癌细胞增殖的作用,可能成为防治胃癌的新靶点。Background： Prostaglandin E2（ PGE2） could promote the proliferation of tumor cells,microRNA-21（ miR-21） could inhibit the proliferation of tumor cells,but its signal pathway is still unclear. Aims： To investigate the mechanism of PGE2 on promoting proliferation of gastric cancer cells potentially mediated by miR-21. Methods： Gastric cancer AGS cells were cultured and divided into control group,PGE2 group,anti-miR-21 group and PGE2＋ anti-miR-21 group. Cell proliferation was determined by WST-1 chromatometry. Cell apoptosis rate was detected by flow cytometry. The expression of miR-21 mRNA was detected by RT-PCR. After AGS cells were intervened by Akt specific inhibitor perifosine,cell proliferation was assessed,and expression of PTEN / Akt protein was detected by Western blotting. Results： Compared with control group,survival rate of AGS cells was significantly increased（ P〈0. 05）,apoptosis rate was significantly decreased（ P〈0. 05）,and expression of miR-21 mRNA was significantly increased in PGE2group（ P〈0. 05）. Compared with PGE2 group,survival rate of AGS cells was significantly decreased（ P〈0. 05）,apoptosis rate was significantly increased（ P〈0. 05）,and expression of miR-21 mRNA was significantly decreased in anti-miR-21 group and PGE2＋ anti-miR-21 group（ P〈0. 05）. After intervention with perifosine,survival rate of AGS cells was significantly decreased（ P〈0. 05）,apoptosis rate was significantly increased（ P〈0. 05）,expression of PTEN protein was significantly increased,and expression of p-Akt protein was significantly decreased. Conclusions： MiR-21 mediates the promoting of proliferation of gastric cancer cells by PGE2 through PTEN / Akt pathway,which might become a new target for the prevention and treatment of gastric cancer.

关 键 词：微RNAS 胃肿瘤 前列腺素E类 PTEN/Akt通路 

分 类 号：R735.2[医药卫生—肿瘤]