摘要
目的考察二甲双胍对胃癌细胞增殖和自噬的影响。方法体外实验使用人胃癌细胞AGS、HGC-27,采用二甲双胍处理后,分别用CCK-8法、流式细胞术、蛋白质印迹法检测细胞增殖、凋亡及caspase 3和微管相关蛋白1轻链3(LC3)等蛋白质表达。体内建立AGS细胞裸鼠皮下移植瘤模型,待肿瘤体积约100 mm^(3)时随机分为对照组、氯喹组、二甲双胍组和二甲双胍与氯喹联合组(n=8),分别予生理盐水、氯喹(50 mg/kg)、二甲双胍(100 mg/kg)和二甲双胍联合氯喹灌胃,每日1次,连续3周,其间定期测量并记录肿瘤体积和重量。结果二甲双胍可抑制AGS、HGC-27细胞增殖(IC_(50)分别为5.72和13.32 mmol/L),诱导细胞凋亡(伴caspase 3激活)并激活自噬(LC3-Ⅱ表达水平上升)(均P<0.01);二甲双胍联合氯喹能进一步降低细胞存活率(P<0.01)。体内实验表明,二甲双胍组小鼠的肿瘤体积和重量均低于对照组(均P<0.01),与氯喹联合后肿瘤体积和重量进一步降低(均P<0.01)。结论二甲双胍能通过抑制胃癌细胞增殖、诱导凋亡同时激活保护性自噬抑制肿瘤生长,且与自噬抑制剂氯喹联合使用可在体内外进一步增强其抗瘤效果。
Objective To investigate the effects of metformin on proliferation and autophagy in gastric cancer cells.Methods Human gastric cancer cell lines AGS and HGC-27 were treated with metformin in vitro,and the cell proliferation,apoptosis and protein expression of cysteine aspartic acid specific protease 3(caspase 3)and microtubule-associated protein 1 light chain 3(LC3)were detected by cell counting kit 8 assay,flow cytometry and Western blotting,respectively.In vivo,a nude mouse model of subcutaneous xenograft tumor was established using AGS cells.When tumor volume reached approximately 100 mm^(3),mice were randomly assigned to 4 groups(n=8):control group,chloroquine group,metformin group,or metformin combined with chloroquine group.Mice were intragastrically administered normal saline,chloroquine(50 mg/kg),metformin(100 mg/kg),and metformin plus chloroquine daily for 3 consecutive weeks,respectively.Tumor volume and weight were measured and recorded regularly during the treatment.Results Metformin inhibited the proliferation of AGS and HGC-27 cells with half inhibitory concentrations of 5.72 and 13.32 mmol/L,respectively,induced apoptosis accompanied by caspase 3 activation,and triggered autophagy indicated by elevated LC3-Ⅱexpression(all P<0.01).Combined treatment with metformin and chloroquine further reduced cell viability(P<0.01).In vivo experiments showed that tumor volume and weight were significantly lower in the metformin group than those in the control group(both P<0.01),and further reduction was observed following combined treatment with chloroquine(both P<0.01).Conclusion Metformin suppresses gastric cancer growth by inhibiting cell proliferation,inducing apoptosis,and activating protective autophagy,and combined treatment with the autophagy inhibitor chloroquine further enhances its antitumor efficacy in vitro and in vivo.
作者
王寒
葛明湃
崔璐
徐俊
印慨
WANG Han;GE Mingpai;CUI Lu;XU Jun;YIN Kai(Department of Gastrointestinal Surgery,The First Affiliated Hospital of Naval Medical University(Second Military Medical University),Shanghai 200433,China)
出处
《海军军医大学学报》
北大核心
2026年第4期511-517,共7页
Academic Journal of Naval Medical University
基金
上海市科学技术委员会医学科技创新研究计划(21Y11913100)。
关键词
二甲双胍
胃肿瘤
自噬
细胞增殖
细胞凋亡
肿瘤治疗
metformin
stomach neoplasms
autophagy
cell proliferation
apoptosis
tumor therapy
