Metformin Induces Apoptosis And Autophagy In Bladder Cancer Cells

OBJECTIVE:To investigate the prognostic factors of non-muscle invasive bladder cancer(NMIBC)after transurethral resection of bladder tumor(TURBt)and the specific mechanism of action of metformin against bladder cancer.METHODS:Regression analysis of clinical records of 269 patients who underwent transurethral resection of bladder tumor in our hospital from January 2013 to December 2017.Patients were divided into 3 groups according to non-diabetic group(NDM),diabetes mellitus without metformin group(DMNMET),and metformin group(DMMET)for diabetes.Kruskal-Wallis H test was used for comparison among different measurement datas,and independent sample chi-squares were used for comparison among different counting datas.Kaplan-Meier method was used to map the survival curves of three groups of recurrence-free survival time(RPS),progression-free survival time(PFS),total survival time(OS)and tumor-specific death time(CSS).Log-rank statistical method was used for comparison among the groups.Basic experiment:CCK-8,scratch test and colony formation assay were used to detect the effect of metformin on the proliferation,migration and clonality of bladder cancer T24.Flow cytometry was used to detect the apoptosis of bladder cancer T24 cells induced by metformin.Western blotting detects protein expression.RESULTS:There was a statistically significant difference in the RPS survival curve between the NDM group and the DMNMET group(P<0.01).There also was a statistically significant difference in the RFS survival curve between the DMNMET group and the DMMET group(P<0.01).PFS between the NDM group and the DMNMET group.Survival curves were statistically significant(P<0.01).There was a statistically significant difference in the PFS survival curve between the DMNMET group and the DMMET group(P<0.01).Metformin inhibited the migration and clonality of bladder cancer T24 and inhibited the proliferation of T24 cells in a time-and concentration－dependent manner.Metformin down-regulated the expression of BAX and PARP-1 on apoptotic pathways and P62 on autophagy pathwayin T24 cells.Conclusion:Metformin contributes to the prognosis of patients with non-muscle invasive bladder cancer.It can induce anti-cancer effect by inducing apoptosis and autophagy in T24 cells.