解放军医学杂志2018，Vol.43Issue(1)：7-11,5.DOI:10.11855/j.issn.0577-7402.2018.01.02
二甲双胍对ALDH+胃癌干细胞的抑制作用及其机制
Inhibitory effect of metformin on aldehyde dehydrogenase positive gastric cancer stem cells and its mechanism
摘要
Abstract
Objective To investigate the inhibitory effect of metformin (Met) on ALDH positive (ALDH+) gastric cancer stem cells and its mechanism.Methods ALDH+ and ALDH cells were isolated from human gastric cancer cell line MKN45 by flow cytometry.The characteristics of cancer stem cells of ALDH+ cells was verified by self-renewing ability,differentiation capacity experiments and tumorigenicity in nude mice.1mmol/L Met group,5mmol/L Met group and control group (MKN45 cell) were set up.After being acted on MKN45 cell for 48h,the proportion ofALDH+ cells in each group was detected by flow cytometry.RT-PCR test was performed to detect the expression of Oct4,Sox2 and AKT genes in the 3 groups.Results The cell identification showed that the self-renewal ability,differentiation capacity and tumorigenicity of ALDH+ cells were higher than that of ALDH-cells.Drug experiments indicated that the proportion ofALDH+ cells in control group,lmmol/L Met group and 5mmol/L Met group were 36.5％ ± 5.4％,15.6％ ± 1.9％ and 7.6％ ± 1.6％,respectively.The difference between the 3 groups was statistically significant (P＜0.01).RT-PCR revealed that the expressions of Sox2 and AKT genes decreased after Met treatment,and decreased with the increase of Met concentration.The expression of Oct4 gene was higher in 1 mmol/L Met group than in control group,and was lower in 5mmol/L Met group than in control group.Conclusion Met may inhibit the growth ofALDH+ gastric cancer stem cells and the expression ofAKT gene,and can be used as a target drug for the clinical treatment of gastric cancer.关键词
肿瘤干细胞/乙醛脱氢酶/二甲双胍/Oct4/Sox2/AKTKey words
cancer stem cells/aldehyde dehydrogenase/metformin/Oct4/Sox2/AKT分类
医药卫生引用本文复制引用
王一,向勇平,刘丹丹,刘理金,姜伟,李锦毅..二甲双胍对ALDH+胃癌干细胞的抑制作用及其机制[J].解放军医学杂志,2018,43(1):7-11,5.基金项目
国家自然科学基金(81273980)This work was supported by the National Natural Science Foundation of China (81273980) （81273980）
