Metformin promotes apoptosis of rat prolactinoma MMQ cells by inducing autophagy

Objective: To investigate the role of autophagy in metformin-induced apoptosis of pituitary prolactinoma cells.  Methods: The different concentrations of metformin was used to treat prolactinoma MMQ cells for different times. CCK-8 assay was used to detect the proliferation of MMQ cells. FCM was used to detect the apoptosis of MMQ cells. The morphology and quantity of autolysosomes in MMQ cells were detected by transmission electron microscopy. After MMQ cells were treated with metformin and/or autophagy inhibitor 3-methyladenine (3-MA), the expressions of mammalian target of rapamycin (mTOR)-autophagy-apoptotic signaling pathway-related proteins were detected by Western blotting. Results: Metformin significantly inhibited the proliferation of MMQ cells (P < 0.05), and induced the apoptosis of MMQ cells (P < 0.05). Metformin induced autophagy, and the number of autophagic bodies in metformin-treated MMQ cells was significantly increased (P < 0.05). Autophagy inhibitor 3-MA significantly inhibited the expressions of microtubule-associated protein light chain 3-Ⅱ (LC3-Ⅱ), Beclin 1 and poly (ADP-ribose) polymerase (PARP) induced by metformin (all P < 0.05). Metformin also significantly inhibited the expressions of phosphorylated mTOR (p-mTOR) and its downstream proteins phosphorylated P70 ribosomal protein S6 kinase (p-P70S6K) and phosphorylated eukaryotic initiation factor 4E binding protein 1 (p-4EBP1) (all P < 0.05). Conclusion: Metformin maybe promote the apoptosis of pituitary prolactinoma cells by down-regulating mTOR activity and inducing autophagy. DOI:10.3781/j.issn.1000-7431.2018.11.151