Additionally, use of metformin contributes to repression of hepatoma cell proliferation and promotion of cell cycle arrest at the G0/G1 phase in a dose-dependent manner through AMP-activated protein kinase and its upstream kinase LKB1 to elevate p21/Cip1 and p27/Kip1 and decline cyclin D1 (32). The gene discussed is CCND1; the disease is hepatocellular carcinoma.