1α,25(OH)_2D_3通过阻滞细胞周期抑制胃癌细胞系增殖

1α,25( OH)_2D_3 inhibits proliferation of gastric cancer cell line by arresting cell cycle

目的研究1α,25(OH)2D3对胃癌细胞增殖和细胞周期的影响,并探讨其相关的作用机制。方法 BGC-823和SGC-7901胃癌细胞系分别给予终浓度为1×10-10～1×10-7mol/L的1α,25(OH)2D3处理72 h,用MTT法检测细胞抑制率;用流式细胞仪检测细胞周期;用RT-qPCR技术检测细胞周期相关基因P21、cyclin D1、cyclin E1和CDK6 mRNA表达。结果 1α,25(OH)2D3对胃癌细胞的增殖抑制率具有浓度依赖性,1α,25(OH)2D3干预导致BGC-823和SGC-7901细胞系G1期细胞比例升高,S期细胞比例降低(P<0.05);1α,25(OH)2D3干预后,BGC-823和SGC-7901胃癌细胞P21 mRNA表达升高(P<0.01),而cyclin D1、cyclin E1和CDK6 mRNA表达降低(P<0.01)。结论 1α,25(OH)2D3抑制胃癌细胞增殖,诱导细胞周期阻滞,可能与上调P21,下调cyclin D1、cyclin E1和CDK6的表达有关。

Objective To observe the effect of 1α ,25 （OH）2D3 on gastric carcinoma cell proliferation anti cell cy- cle progression and to investigate its possible mechanism. Methods Two gastric cancer cell lines BGC-823 and SGC-7901 were treated with 1α,25 （OH）2D3 in a dose dependent manner. Cell proliferation was determined by methyl thiazolyl tetrazolium MTT assay; the cell cycle changes were detected by using flow cytometry ; the expres- sion of genes of P21, cyclin D1, cyclin El and CDK6 related to the cell cycle was analyzed by RT-PCR. Results 1α,25 （OH）2D3 significantly inhibited two gastric cancer cell lines proliferation in a dose dependent fashion, gas- tric cancer cells treated with 1α,25 （OH）2D3 caused significantly cell cycle arrest at GI phase; RT-qPCR showed that 1α ,25 （OH）2D3 significantly increased P21 mRNA, and attenuated cyclin D1, cyclin El, CDK6 mRNA ex- pression in BGC-823, SGC-7901 cells（P〈0.01）. Conclusions 1α,25（OH）2D3 inhibites BGC-823, SGC-7901 cell proliferation and induces cell cycle arresting in G1 phase. The mechanism for the anti-proliferative and cell cy- cle arrest is probably related to overexpression of P21, down-regulated expression of cyclin D1, cyclin El, CDK6.