Min Li, Xiuli Jiang, Tingwei Su, Lei Jiang, Weiwei Zhou, Weiqing Wang
Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (mainland)
Med Sci Monit 2017; 23:3253-3260
Previous studies have clearly demonstrated that metformin inhibits cell proliferation and cell growth in many types of human cancers. Increased survival rates in patients with breast and lung cancer receiving metformin have also been observed. However, the effect of metformin on pheochromocytoma cells remains unexplored.
MATERIAL AND METHODS: Rat pheochromocytoma cells (PC12 cells) were cultured and treated with metformin or vehicle control. Cell proliferation, cell-cycle, apoptosis, genes expression, and the signaling pathways involved were analyzed in PC12 cells.
RESULTS: The metformin treatment reduced cell viability and proliferation in rat pheochromocytoma PC12 cells in a dose- and time-dependent manner. Furthermore, metformin exposure led to an increased apoptosis rate and cell-cycle arrest accompanied with downregulation of Ccna2 and Ccnb2. At the molecular level, the AMPK signaling pathway was activated, whereas the mTOR and ERK1/2 signaling pathways were inhibited by metformin.
CONCLUSIONS: Our data suggest an antiproliferative role of metformin in pheochromocytoma development, which may provide a novel option for future cancer therapy.
Keywords: AMP-Activated Protein Kinases, Cell Proliferation, metformin, Pheochromocytoma, TOR Serine-Threonine Kinases