Previous studies have shown that several mediators, including ERK1/2, E2F1, Akt, PPARγ, FOXP3 and STAT3, regulate Skp2 expression at the transcriptional level.35, 46, 47, 48, 49, 50 Recent studies have also reported that simvastatin can inhibit ERK1/2, Akt and STAT3 expression to suppress tumor cell growth and induce cell apoptosis.51, 52 However, no reports regarding STAT3 and Skp2 regulation in simvastatin-induced growth arrest in HCC are available. This evidence concerns the gene AKT1 and neoplasm.