Study on inhibitory effects and mechanism of amlodipine on human breast carcinoma cell line MCF-7 / 中国药理学通报

ABSTRACT

Aim To observe the effects of amlodipine on cell cycle,cell cycle-related genes and cyclin expression of human breast carcinoma MCF-7 cells.And to probe effects of amlodipine on cell cycle and its mechanism of human breast carcinoma MCF-7 cells.Methods In vitro growth inhibitory effects of amlodip-ine on human breast carcinoma MCF-7 cells were determined by MTT assay,cell cycle distribution was detected by flow cytometry,the Mrna expression levels of cell cycle-related genes cyclinD1 and p21 were treated by RT-PCR,and the protein expression of cell cycle protein cyclinD1 and p21 were assessed by Western blot.Results With dose and time dependently,amlodipine could inhibit the proliferation of human breast carcinoma MCF-7 cells in vitro.The IC_(50) was 14.439 μmol·L~(-1).When breast cancer cells MCF-7 were treated with 7.22 μmol·L~(-1)(1/2 IC_(50)),14.439 μmol·L~(-1)(IC_(50))and 28.88 μmol·L~(-1)(2IC_(50))amlodipine for 48 h,the ratios in the G_0/G_1 phase were significantly increased as compared with control group(P<0.05).Amlodipine inhibited the expression of Mrna and protein of cyclinD1,while increased the expression of Mrna and protein of p21.Conclusions Amlodipine exhibits obvious anti-tumor activities on human breast carcinoma MCF-7 cells and arrest cell cycle in G_1 phase.The mechanism of G_1 phase arresting may be related to modulating the Mrna and protein expression of cell cycle-related gene cyclinD1 and p21.