Zheng et al. showed both in vitro and in vivo that the activation of AMPK by metformin suppressed NF-kB/STAT3 signaling, leading to the inhibition of HCC cell growth [75], while Cai et al. found that metformin treatment inhibited the growth and proliferation of HepG2 and PLC/PRF/5 cells in vitro and of nude mice in vivo through the induction of cell cycle G1/G0 phase arrest and the upregulation of the tumor suppressor proteins p21CIP and p27KIP. This evidence concerns the gene NFKB1 and hepatocellular carcinoma.