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

Huang,Jian; Yang,Guozhen; Huang,Yunzhu; Zhang,Shu

doi:10.3892/or.2017.5848

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

Authors:
- Jian Huang
- Guozhen Yang
- Yunzhu Huang
- Shu Zhang
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Affiliations: Biochemistry Department, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China, Medical Laboratory, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
Published online on: July 24, 2017 https://doi.org/10.3892/or.2017.5848
Pages: 1845-1850

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Abstract

The inhibitory effects of 1,25(OH)2D3 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)2D3 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)2D3 inhibited cell proliferation in vitro. Western blotting and real-time PCR indicated that 1,25(OH)2D3 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)2D3 on PTEN gene expression. The influence of 1,25(OH)2D3 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)2D3 treatment, was promoted by HDAC2 overexpression. These findings revealed that 1,25(OH)2D3 inhibited cell growth possibly by HDAC2-mediated PTEN upregulation, Akt deactivation, and inhibition of the PI3K/Akt signaling pathway.

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