1,25-二羟维生素D3对子宫内膜癌HEC-1-A细胞增殖与S期激酶相关蛋白及抑癌基因p27表达的影响

Objective To investigate the expressions of vitamin D receptor (VDR) in endometrial carcinoma cell HEC-1-A;to study the effect of 1,25-(OH)2D3 on prolifetation of human endometrial carcinoma cell HEC-1-A and the mechanism of detecting the expression of S-phase kinase associated protein 2 ( Skp2 ) and p27 gene.Methods Expressions of VDR in human endometrial carcinoma cell HEC-1-A were detected by immunohistochemical method. HEC-1-A human endometrial carcinoma cell line were cultured in vitro and treated with different concentrations of 1,25-( OH)2D3 for 1-5 days. Cell proliferation was evaluated by CCK-8 method, distribution of cell cycle were determined by flow cytometry. The expression level of Skp2/p27 mRNA was examined by real-time quantitative polymerase chain reaction (RT-qPCR). The expression level of Skp2/p27 protein was finally detected by Western blotting. Results (10-8-10-6) mol/L 1,25-(OH)2D3 inhibited the proliferation of HEC-1-A cell line,and inhibitory rate was positively associated with concentration of 1,25-( OH)2D3 and treatment time. 1,25-(OH)2D3 increased the rates of G0/G1, decreased the rates of S and G2/M and also decreased cells PI (P ＜0.01 ). The mRNA and protein expression of Skp2 in HEC-1-A cell lines after 1,25 (OH)2 D3 treatment decreased.The level of p27 mRNA was decreased but the level of p27 protein was significantly increased. Conclusions 1 ,25-(OH)2D3 can inhibit the growth of HEC-1-A cell line. It may inhibit cancer cell proliferation through down-regulation of Skp2 gene and increase p27 stability by decreasing the abundance of Skp2.

The effect of 1,25-( OH)2D3 on proliferation and expression of Skp2/p27 in endometrial carcinoma cell HEC-1-A