MicroRNA-21通过PTEN/Akt通路介导前列腺素E2促进胃癌细胞的增殖

摘要

背景：已有研究证实前列腺素 E2（PGE2）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 PGE2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、PGE2组、anti-miR-21组、PGE2+ 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，PGE2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 PGE2组相比，anti-miR-21组、PGE2+ 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 PGE2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 PGE2 group(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.