姜黄素通过下调PI3K/Akt/mTOR信号通路蛋白表达对胃癌MGC-803细胞增殖和侵袭的抑制作用  

Inhibitory effect of curcumin on proliferation and invasion of gastric cancer MGC-803 cells by down-regulating PI3K/Akt/mTOR signaling pathway protein expression

作　　者：孙逸飞 李迪诺 王玉彬 SUN Yifei;LI Dinuo;WANG Yubin(Graduate School,Jinzhou Medical University,Jinzhou 121000,China;Department of General Surgery and Gastroenterology,First Affiliated Hospital,Jinzhou Medical University,Jinzhou 121000,China)

机构地区：[1]锦州医科大学研究生院,辽宁锦州121000 [2]锦州医科大学附属第一医院普外胃肠科,辽宁锦州121000

出　　处：《吉林大学学报（医学版）》2023年第2期332-340,共9页Journal of Jilin University：Medicine Edition

基　　金：国家卫健委医药卫生科技发展项目(WA2021RW25);辽宁省科技厅自然科学基金项目(20170540334)。

摘　　要：目的:观察姜黄素对胃癌MGC-803细胞体内外增殖和侵袭的作用,探讨磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B (Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的作用机制。方法:胃癌MGC-803细胞分为对照组、低剂量(10μmol·L^(-1))姜黄素组、中剂量(20μmol·L^(-1))姜黄素组和高剂量(40μmol·L^(-1))姜黄素组。采用CCK-8法检测各组MGC-803细胞增殖能力,Transwell法检测各组MGC-803细胞侵袭能力,流式细胞术检测各组MGC-803细胞凋亡率。采用MGC-803细胞建立胃癌移植瘤模型,分别使用低剂量(0.5 mg·kg^(-1))、中剂量(1.0 mg·kg^(-1))和高剂量(2.0 mg·kg^(-1))姜黄素处理小鼠,观察姜黄素对各组小鼠肿瘤生长的抑制作用,TUNEL法检测各组小鼠移植瘤组织中肿瘤细胞的凋亡情况,Western blotting法检测各组小鼠移植瘤组织中PI3K/Akt/mTOR信号通路蛋白表达水平。结果:与对照组比较,不同剂量姜黄素组细胞增殖能力和侵袭细胞数明显降低(P<0.05),细胞凋亡率明显升高(P<0.05);低剂量姜黄素组中的胃癌MGC-803细胞增殖能力和侵袭细胞数明显高于高剂量姜黄素组(P<0.05),细胞凋亡率明显低于高剂量姜黄素组(P<0.05)。与对照组比较,不同剂量姜黄素组小鼠移植瘤体积明显缩小(P<0.05)。对照组小鼠移植瘤的细胞凋亡率较低,中剂量姜黄素组小鼠移植瘤的细胞凋亡率明显高于低剂量姜黄素组(P<0.05),而高剂量姜黄素组小鼠移植瘤的细胞凋亡率明显高于中剂量姜黄素组(P<0.05)。与对照组比较,不同剂量姜黄素组小鼠移植瘤组织中PI3K、磷酸化Akt (p-Akt)和磷酸化mTOR (p-mTOR)蛋白表达水平均明显降低(P<0.05);低剂量姜黄素组小鼠移植瘤组织中PI3K、p-Akt和p-mTOR蛋白表达水平明显低于中剂量姜黄素组(P<0.05);高剂量姜黄素组小鼠移植瘤组织中PI3K、 p-Akt和p-mTOR蛋白表达水平明显低于中剂量姜黄素组(P<0.05)。结论:姜黄素可有效抑制肿瘤生长,降低其侵袭Objective:To observe the effect of curcumin on proliferation and invasion of the gastric cancer MGC-803 cells in vitro and in vivo,and to discuss the mechanism of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian rapamycin target protein(mTOR)signaling pathway.Methods:The gastric cancer MGC-803 cells were divided into control group,low dose(10μmol·L^(-1))of curcumin group,middle dose(20μmol·L^(-1))of curcumin group,and high dose(40μmol·L^(-1))of curcumin group.The proliferation abilities of the MGC-803 cells in various groups were detected by CCK-8 method;the invasion abilities of the MGC-803 cells in various groups were detected by Transwell method;the apoptotic rates of the MGC-803 cells were detected by flow cytometry.The MGC-803 cells were used to establish the gastric cancer transplanted tumor model and the mice were treated with low(0.5 mg·kg^(-1)),middle(1.0 mg·kg^(-1)),and high(2.0 mg·kg^(-1))doses of curcumin,and the inhibitory effect of curcumin on the tumor growth of the mice in various groups was observed.TUNEL method was used to detect the apoptosis of the tumor cells in transplanted tumor tissue of the mice in various groups;the expression levels of PI3K-Akt-mTOR signaling pathway proteins in transplacted tumor tissue of the mice in various groups were detected by Western blotting ththod.Results:Compared with control group,the proliferation abilities and number of invasion cells in different doses of curcumin groups were significantly decreased(P<0.05),and the apoptotic rates were significantly increased(P<0.05);the cell proliferation ability and the number of invasion cells in low dose of curcumin group were significantly higher than those in high dose of curcumin group(P<0.05),and the apoptotic rate was significantly lower than that in high dose of curcumin group(P<0.05).Compared with control group,the volumes of transplanted tumor of the mice in different doses of curcumin groups were significantly decreased(P<0.05).The apoptotic rate of the cells in transplanted tumor

关 键 词：姜黄素 胃肿瘤 磷脂酰肌醇3-激酶 蛋白激酶B 哺乳动物雷帕霉素靶蛋白 细胞增殖 细胞侵袭 细胞凋亡 

分 类 号：R735.2[医药卫生—肿瘤]