Inhibitory effect of metformin on aldehyde dehydrogenase positive gastric cancer stem cells and its mechanism / 解放军医学杂志

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.