CDK4 and cancer: 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.