紫草素调控PI3K/Akt/mTOR通路对人胃癌MGC803细胞自噬和凋亡的影响  

Effect of Shikonin on autophagy and apoptosis of human gastric cancer MGC803 cells by regulating PI3K/Akt/mTOR

作　　者：张欣[1] 霍浩然[1] 张振翼[1] 尹立阳 房娉平[1] 袁增江[1] ZHANG Xin;HUO Hao-ran;ZHANG Zhen-yi;YIN Li-yang;FANG Ping-ping;YUAN Zeng-jiang(Department of General Surgery,Handan Central Hospital,Handan 056000,China)

机构地区：[1]邯郸市中心医院普外三科,河北邯郸056000

出　　处：《中国现代普通外科进展》2023年第7期511-515,共5页Chinese Journal of Current Advances in General Surgery

基　　金：河北省邯郸市科学技术研究与发展计划项目(19422083016ZC)。

摘　　要：目的:研究紫草素对人胃癌MGC803细胞自噬和凋亡的影响及作用机制。方法:取对数生长期MGC803细胞,设空白对照组、紫草素组、紫草素+IGF-1(PI3K激活剂)组、紫草素+LY294002(PI3K抑制剂)组。药物干预24 h后,CCK-8法检测细胞增殖抑制率,流式细胞术检测细胞凋亡,GFP-LC3质粒转染法观察细胞自噬小体,Western blot法检测磷脂酰肌醇3激酶(PI3K)、p-PI3K、蛋白激酶B(Akt)、p-Akt、哺乳动物雷帕霉素靶蛋白(mTOR)、p-mTOR、Caspase-3、cleaved Caspase-3、LC3、Beclin-1的表达。结果:与空白对照组比较,紫草素组细胞增殖抑制率、凋亡率升高(P<0.05),自噬小体数量明显增多,PI3K、Akt、mTOR磷酸化水平降低(P<0.05),cleaved Caspase-3/Caspase-3、LC3-Ⅱ/LC3-Ⅰ及Beclin-1表达量升高(P<0.05)。IGF-1可明显逆转紫草素对MGC803细胞增殖抑制、凋亡、自噬,PI3K、Akt、mTOR磷酸化和cleaved Caspase-3/Caspase-3、LC3-Ⅱ/LC3-Ⅰ比值等的调控作用,LY294002可明显加强紫草素对MGC803细胞上述调控作用。结论:紫草素可促进MGC803细胞自噬和凋亡,可能与抑制PI3K/Akt/mTOR通路有关。Objective:To study the effect of Sshikonin on autophagy and apoptosis of human gastric cancer MGC803 cells and its mechanism.Methods:The MGC803 cells in logarithmic growth phase were divided into blank control group,Shikonin group,Shikonin+IGF-1(PI3K activator)group and Shikonin+LY294002(PI3K inhibitor)group.24 h after drug intervention,the cell proliferation inhibition rate was detected by CCK-8,the cell apoptosis was detected by flow cytometry,the autophagosomes was observed by transfection with GFP-LC3.The expression of PI3K,p-PI3K,Akt,p-Akt,mTOR,p-mTOR,Caspase-3,cleaved Caspase-3,LC3,Beclin-1 were detected by Western blot.Results:Compared with blank control group,the cell proliferation inhibition rate and apoptosis rate in Shikonin group were increased,the number of autophagosomes was increased,the phosphorylation level of PI3K,Akt,mTOR was decreased,the cleaved Caspase-3/Caspase-3,LC3-Ⅱ/LC3-Ⅰ and Beclin-1 expression were increased(P<0.05).IGF-1 could reverse the effect of Shikonin on proliferation inhibition,apoptosis and autophagy,PI3K,Akt,mTOR phosphorylation and the ratio of cleaved Caspase-3/Caspase-3,LC3-Ⅱ/LC3-Ⅰ;LY294002 could enhance the regulatory effects of Shikonin on MGC803 cells.Conclusion:Shikonin can promote autophagy and apoptosis of human gastric cancer MGC803 cells,which may be related to the inhibition of PI3K/Akt/mTOR pathway.

关 键 词：紫草素 胃肿瘤 PI3K/Akt/mTOR通路 自噬 凋亡 

分 类 号：R735.2[医药卫生—肿瘤]