And our findings indicate that the depletion of HMGB1 and the application of PI3K/Akt pathway inhibitors ly294002 have the same effect, both can make cancer cells blocked at G0/G1 stage resulting in apoptosis induction and inhibition of cancer cell proliferation through decreasing the expression of Cyclin D1 and CDK4 and improving P16, however, IGF1 has the opposite effect. Here, CCND1 is linked to cancer.