Inhibitory effects of 1,25(OH)2D3 on the proliferation of hepatocellular carcinoma cells through the downregulation of HDAC2

The inhibitory effects of 1,25(OH)(2)D-3 on the proliferation of a variety of cancer cell lines have been extensively reported. However, the underlying mechanisms remain largely unknown. In the present study, the effects of 1,25(OH)(2)D-3 on the in vitro proliferation of human hepatocellular carcinoma HepG2 cells and the mechanism involved were investigated. Flow cytometry and MTT assay revealed that 1,25(OH)(2)D-3 inhibited cell proliferation in vitro. Western blotting and real-time PCR indicated that 1,25(OH)(2)D-3 upregulated the expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and attenuated that of histone deacetylase 2 (HDAC2). Knockdown of HDAC2 completely mimicked the effects of 1,25(OH)(2)D-3 on PTEN gene expression. The influence of 1,25(OH)(2)D-3 on PTEN expression was reversed in the cells treated with a recombinant pEGFP-LV2-HDAC2 plasmid. Akt phosphorylation, which was downregulated by 1,25(OH)(2)D-3 treatment, was promoted by HDAC2 overexpression. These findings revealed that 1,25(OH)(2)D-3 inhibited cell growth possibly by HDAC2-mediated PTEN upregulation, Akt deactivation, and inhibition of the PI3K/Akt signaling pathway.