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作 者:刘景华[1] 赵阳 李宾[1] 于雅丽[1] 王万里[1] 任艳红 LIU Jinghua;ZHAO Yang;LI Bin;YU Yali;WANG Wanli;REN Yanhong(Department of Gastroenterology,Zhengzhou Seventh People's Hospital,Zhengzhou 450000,China;Pharmaceutical Department,Jinan People's Hospital,Jinan 271100,China)
机构地区:[1]郑州市第七人民医院消化内科,河南郑州450000 [2]济南市人民医院药剂科,山东济南271100
出 处:《药物评价研究》2020年第12期2444-2449,共6页Drug Evaluation Research
摘 要:目的探究甘草次酸对胃癌SGC7901细胞增殖、凋亡及PI3K-Akt-mTOR通路的影响。方法体外培养胃癌SGC7901细胞,分为对照组和甘草次酸低、中、高浓度(12.5、25.0、50.0μmol/L)组,药物处理24、48、72 h后,CCK-8法检测细胞增殖情况;药物处理48 h后,流式细胞仪检测细胞周期分布及细胞凋亡情况;Western blotting检测凋亡相关蛋白Bcl-2、Bax、cleaved Caspase-3以及PI3K-Akt-mTOR信号通路中磷酸化PI3K、Akt、mTOR蛋白表达水平。结果甘草次酸低、中、高浓度组胃癌SGC7901细胞增殖受到明显抑制,并呈时间和剂量相关性(P<0.05)。与对照组比较,甘草次酸低、中、高浓度组胃癌SGC7901细胞G0/G1期细胞比例显著降低(P<0.05),G2/M期细胞比例及凋亡率显著升高(P<0.05),Bax、cleaved Caspase-3蛋白表达水平显著升高(P<0.05),Bcl-2、p-PI3K、p-Akt、p-mTOR蛋白表达水平显著降低(P<0.05)。结论甘草次酸可抑制胃癌SGC7901细胞增殖,促进其凋亡,其机制可能与抑制PI3K-Akt-mTOR信号通路激活有关。Objective To investigate the effects of glycyrrhetinic acid on proliferation,apoptosis and phosphatidylinositol 3-kinase(PI3K)-serine/threonine protein kinase(Akt)-mammalian target of rapamycin(mTOR)(PI3K-Akt-mTOR)pathway of gastric cancer SGC7901 cells.Methods Gastric cancer SGC7901 cells were cultured in vitro,and divided into control group,low,medium and high concentration(12.5,25.0 and 50.0μmol/L)groups of glycyrrhetinic acid.Cells proliferation was detected by CCK-8;Cells cycle distribution and apoptosis were detected by flow cytometry;The apoptosis-associated proteins Bcl-2,Bax,cleaved Caspase-3,and phosphorylation of PI3K,Akt and mTOR protein PI3K-Akt-mTOR signaling pathway expression levels were analysed by Western blotting.Results The proliferation of gastric cancer SGC7901 cells in low,medium and high concentrations groups of glycyrrhetinic acid was significantly inhibited in a time-and dose-dependent manner(P<0.05).Compared with the control group,in the low,middle and high concentration groups of glycyrrhetinic acid,the proportion of G0/G1 phase cells of gastric cancer SGC7901 cells significantly decreased(P<0.05),and the proportion of G2/M phase cells and the apoptosis rate significantly increased(P<0.05).The expression levels of Bax and cleaved Caspase-3 proteins significantly increased(P<0.05),and the expression levels of Bcl-2,p-PI3K,p-Akt and p-mTOR proteins significantly decreased(P<0.05).Conclusion Glycyrrhetinic Acid can inhibit the proliferation and promote the apoptosis of gastric cancer SGC7901 cells,which may be related to the inhibition of PI3K-Akt-mTOR signaling pathway.
关 键 词:甘草次酸 胃癌细胞 增殖 凋亡 磷脂酰肌醇3-激酶 丝氨酸/苏氨酸蛋白激酶 哺乳动物雷帕霉素靶蛋白
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