Effect Of Metformin On Proliferation And Apoptosis Of Rat Prolactinoma MMQ Cells And Related Mechanisms

Objective: To investigate the effect of metformin on the cell proliferation,cell cycle and apoptosis of Rat Prolactinoma MMQ cells in vitro and related molecular mechanisms.Methods: The MMQ cells were treated with different concentrations of metformin(1.25,2.5,5,10,20 mmol/L)for 48 hours.CCK-8 assay was used to assess the cell proliferation ability;Flow cytometry was used to analyze the cell cycle distribution and apoptosis;Western blotting was performed to detect the expressions of AMPK,p-AMPK,m TOR,p-m TOR,IGF-1R,ERK1/2,p-ERK1/2,AKT,p-AKT,P21,CDK4,cyclin D1,caspase-3,cleaved caspase-3(c-caspase-3),Bcl-2 and BAX.Results: Compared with the control group,metformin inhibited cell proliferation,induced cell cycle arrest in the G0/G1 phase and promoted cell apoptosis in MMQ cells.The expressions of P21 and c-caspase-3 increased,meanwhile,the expressions of CDK4,cyclin D1,caspase-3 and Bcl-2 decreased by metformin.Besides,the expression of p-AMPK was elevated,but p-m TOR was reduced.Futhermore,the expressions of IGF-1R,p-AKT and p-ERK descended after metformin treatment.Conclusion: Metformin could inhibit cell proliferation,induce cell cycle arrest and apoptosis in MMQ cells.AMPK /m TOR and IGF-1R signaling pathway may play an important role on the anti-proliferative and apoptotic effects of metformin on MMQ cells.