氨氯地平对人乳腺癌细胞MCF-7细胞周期和周期蛋白表达的影响及其调控机制

Effect of Amlodipine on Cell Cycle and Cyclin Expression of Human Breast Cancer MCF-7 Cells and Regulation Mechanism of The Effect

目的探讨氨氯地平对人乳腺癌细胞MCF-7细胞周期及周期蛋白表达的影响及其调控机制。方法以不同浓度的氨氯地平处理对数生长期的MCF-7细胞,MTT法检测细胞增殖水平;流式细胞仪分析细胞周期;免疫细胞化学法检测细胞周期蛋白cyclinD1、p21和p53的表达。结果氨氯地平呈剂量和时间依赖性抑制MCF-7细胞增殖,IC50为14.439μmol/L;经7.220μmol/L(0.5IC5)0、14.439μmol/L(1IC5)0和28.880μmol/L(2IC50)氨氯地平处理48h,G0/G1期细胞比例较对照组明显增高;经7.220μmol/L氨氯地平处理48h,MCF-7细胞中cyclinD1蛋白表达降低,p21和p53蛋白表达升高。结论氨氯地平对MCF-7细胞的增殖具有抑制作用,此作用与使细胞阻滞于G1期有关,其机制与调控细胞周期相关蛋白cyclinD1、p21和p53的表达有关。

Objective To investigate the effect of amlodipine on cycle and cyclin expression of human breast cancer MCF-7 cells as well as the regulation mechanism of the effect.Methods The MCF-7 cells at logarithmic growth phase were treated with amlodipine at various concentrations.The cell proliferation level was determined by MTT method,the cell cycle was measured by flow cytometry,and the expressions of cyclinD1,p21 and p53 were determined by immunocytochemical method.Results Amlodipine showed dose-and time-dependent inhibitory effect on the proliferation of MCF-7 cells,with a IC50 of 14.439μmol/L.After treatment with amlodipine at concentrations of 7.220（0.2 IC50）,14.439（1 IC50）and 28.880μmol/L（2 IC5）0for 48 h,the percentage of MCF-7 cells at G0/G1 phase increased significantly as compared with those of control.The expression level of cyclinD1 in MCF-7 cells after treatment with 7.220μmol/L amlodipine for 48 h decreased,while those of p21 and p53 increased.Conclusion Amlodipine showed inhibitory effect on the proliferation of MCF-7 cells,which was associated with G1 phase arresting.However,the mechanism of G1 phase arresting was correlated with the regulation of expressions of cyclinD1,p21 and p53.