环境与职业医学2017，Vol.34Issue(5)：403-409,7.DOI:10.13213/j.cnki.jeom.2017.16719
LY294002抑制PI3K/AKT/mTOR信号通路对胃癌细胞MGC-803的影响
Effects of inhibiting PI3K/AKT/mTOR signaling pathway by LY294002 on gastric cancer MGC-803 cells
摘要
Abstract
[Objective] To investigate the effects of phosphoinositide 3-kinase (PI3K) inhibitor LY294002 on the activity of PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway,as well as relevant biological behavioural alteration of gastric cancer MGC-803 cells.[Methods] Human gastric cancer MGC-803 cells were treated with LY294002 at 12.5,25,and 50 μmol/L (experimental groups).The mRNA expressions of key signal molecules in PI3K/AKT/mTOR signaling pathway including PTEN,PI3K,AKT,mTOR,P70S6K,and 4EBP,as well as related protein expressions,were detected by quantitative real-time PCR and Western blot,respectively.The growth-inhibiting effects of LY294002 on MGC-803 cells were detected by MTT assay.The effects on cell cycle and cell apoptosis were detected by flow cytometry.[Results] Compared with the control (DMSO) group,LY294002 significantly regulated the mRNA expressions of PI3K,PTEN,AKT,mTOR,4EBP,and P70S6K (P ＜0.05),and the mRNA expression levels of AKT,mTOR,4EBP,and P70S6K were declined with LY294002 concentration increasing.LY294002 significantly down-regulated the protein expression of AKT,p-mTOR,p-70S6K,and p-AKT,which showed a declining trend with LY294002 concentration increasing.The MTT assay results showed significant inhibiting effects of LY294002 on MGC-803 cells' proliferation as the proliferation rate increased with LY294002 concentration reducing (F=26.15,P＜0.01).The results of flow cytometry showed that the proportions of G0/G1 cells (F=358.594,P＜0.001) and the apoptosis rates (F=4.929,P＜0.05) of the LY294002 groups were higher than those of the control group in a dose-dependent manner.[Conclusion] LY294002 may inhibit the key signaling molecules of PI3K/AKT/mTOR signaling pathway in MGC-803 cells to varied degrees.The mRNA expressions of AKT,mTOR,4EBP,and P70S6K and related phosphorylated proteins show a declining pattern with LY294002 concentration increasing.Besides,LY294002 could decrease cell proliferation rate,change the proportion of cell cycle,and increase apoptosis rate.关键词
MGC-803细胞/PI3K/AKT/mTOR信号通路/LY294002/胃癌Key words
MGC-803 cell/PI3K/AKT/mTOR signaling pathway/LY294002/gastric cancer分类
医药卫生引用本文复制引用
徐余超,陈晓伟,孙海翔,赵颖,张文文,刘梦琪,沈孝兵..LY294002抑制PI3K/AKT/mTOR信号通路对胃癌细胞MGC-803的影响[J].环境与职业医学,2017,34(5):403-409,7.基金项目
国家自然科学基金项目(编号:81172619,81472940) （编号:81172619,81472940）
