1,25(OH)2D3 induced apoptosis of human hepatocellular carcinoma cells in vitro and inhibited their growth in a nude mouse xenograft model by regulating histone deacetylase 2

The aim of this study was to evaluate the effects of 1,25(OH)2D3 on the apoptosis of human hepatocellular carcinoma (HCC) cells. The effects of 1,25(OH)2D3 on the proliferation and apoptosis of human HCC cells by regulating histone deacetylase 2 (HDAC2) were assessed by MTT assay and flow cytometry. The effects of 1,25(OH)2D3 on the expressions of related proteins in the apoptosis pathway by regulating HDAC2 as well as the mechanism were studied by Western blot and quantitative real-time PCR. A nude mouse model of HCC xenograft was established. A control group, a 1,25(OH)2D3 treatment group, a 1,25(OH)2D3 + HDAC2 overexpression group, an HDAC2 interference group and an HDAC2 overexpression group were set. The tumor volume was recorded, and histopathological changes were observed by HE staining. 1,25(OH)2D3 inhibited the proliferation of HepG2 cells and induced their apoptosis. Overexpression of HDAC2 attenuated the inhibitory effects of 1,25(OH)2D3 on the proliferation of HepG2 cells and its ability to induce apoptosis. In the 1,25(OH)2D3 + HDAC2 overexpression group, the expressions of p53, Bax, DR5 and caspase 8 were significantly lower but the expression of Bcl-2 was significantly higher than those of the 1,25(OH)2D3 treatment group (P < 0.05). Compared with the control group, 1,25(OH)2D3 treatment and HDAC2 interference groups had significantly decreased tumor volumes and promoted apoptosis of HCC cells in tumor tissues. Overexpression of HDAC2 weakened the inhibitory effects of 1,25(OH)2D3 on tumor volume and its ability to induce apoptosis in tissues. A large area of tumor cells underwent necrosis in 1,25(OH)2D3 treatment and HDAC2 interference groups. In the 1,25(OH)2D3 + HDAC2 overexpression group, both the area of necrosis and cell volume decreased. In conclusion, 1,25(OH)2D3 inhibited the proliferation of HCC cells and induced their apoptosis by down-regulating the expression of HDAC2, up-regulating p53, and regulating its downstream mitochondria-mediated pathway and the exogenous DR-mediated pathway.