HIF1A and cancer: These studies showed that the mechanism of metformin may be associated with the following observations: (1) metformin inhibits mTOR activation by AMPK-dependence in different cancers [37,38,39]; (2) mTOR signaling regulates P70S6K signaling in cervical carcinoma cells [40]; (3) metformin induce intrinsic apoptosis via the inhibition of the HIF1α/PKM2 signaling pathway [41]; and (4) metformin is also a poisoner of mitochondria by impairing the function of complex I [42], leading to the increased aerobic glycolysis as compensation.