Metabolic switching in the hypoglycemic and antitumor effects of metformin on high glucose induced HepG2 cells

Metformin, a widely prescribed drug for the management of type 2 diabetes mellitus, has potential anticancer effect. Diabetes patients regularly taking metformin have been reported with decreased cancer risk and improved cancer prognosis in recent years. A cell model of high glucose induced HepG2 cells was conducted to mimic insulin resistance, and a 1H NMR-based metabolomics approach in conjunction with molecular biology was performed to investigate the metabolic changes of high glucose induced HepG2 cells in response to different doses of metformin treatment and to study the differences and links between hypoglycemic and antitumor effects of metformin. Metformin with hypoglycemic effect rectified glucose metabolic imbalance and regulated oxidative stress, energy and amino acid metabolism. Metformin inhibited tumor cell proliferation and induced apoptosis through activation of AMPK/mTOR pathway and further influencing energy metabolism, phospholipid metabolism and glucose catabolism. The integrated metabolomics approach showed its potential in clarifying the different action on metformin treatment and understanding the pleiotropic effect of metformin.