Aurora A激酶抑制剂MLN8237对乳腺癌细胞增殖及凋亡的影响  

Effects of Aurora kinase inhibitor on proliferation and apoptosis of breast cancer cells

作　　者：张月[1] 孙光源 姜伟华[1] 孙健[1] 范敬静[1] 信国峰[1] 宋文丽[1] 武雪亮[1] 张志生[1] 

机构地区：[1]河北北方学院附属第一医院,河北张家口075000

出　　处：《山东医药》2017年第26期13-16,共4页Shandong Medical Journal

基　　金：河北省医学科学研究重点课题(ZD20140243)

摘　　要：目的观察Aurora A激酶抑制剂MLN8237对体外培养的人乳腺癌细胞增殖和凋亡的影响。方法取乳腺癌MCF7细胞分为两组,观察组分别加入0.001、0.01、0.1、1、10μmol/L MLN8237,对照组不加MLN8237。用MTT法检测各组细胞增殖抑制率,流式细胞术检测细胞周期,Western blotting法检测磷酸化Aurora A(p-Aurora A)激酶和凋亡相关蛋白Bcl-2、Bax及细胞周期相关蛋白Cyclin B1的表达,AnnexinⅤ-FITC与PI双染法检测细胞凋亡率。结果观察组随MLN8237浓度和培养时间增加,细胞增殖抑制率增加,10μmol/L MLN8237作用48 h的细胞增殖抑制率最高,0.01、0.1、1、10μmol/L MLN8237作用24、48 h的细胞增殖抑制率均高于对照组(P均<0.05)。与对照组比较,观察组随MLN8237浓度增加,G0/G1期、S期细胞比例降低,G2/M期细胞比例升高。观察组各浓度与对照组比较差异均有统计学意义(P均<0.05)。与对照组比较,观察组随MLN8237浓度增加,p-Aurora A激酶、Bcl-2表达降低,Bax表达升高。与对照组比较,观察组随MLN8237浓度增加,细胞凋亡率增加,10μmol/L MLN8237作用24 h的细胞凋亡率最高(P均<0.05)。结论 MLN8237能够抑制乳腺癌细胞MCF-7增殖,并诱导细胞凋亡。Objective To investigate the effects of Aurora kinase inhibitor MLN8237 on proliferation and apoptosis of human breast cancer cells cultured in vitro. Methods MCF7 cells were divided into two groups,including the control group（ without MLN8237） and the observation group（ added with 0. 001,0. 01,0. 1,1,and 10 μmol/LMLN8237）. The cell proliferation inhibitory rate was examined by MTT assay. Cell cycle of MCF7 cells was determined by flow cytometry. The expression levels of phosphorate-Aurora A（ p-Aurora A）,apoptosis-related proteins Bcl-2,Bax,and cell cycle-related Cyclin B1 protein were detected by Western blotting. The apoptotic rate was tested by Annexin V-FITC and PI staining. Results MLN8237（ 0. 01,0. 1,1,10 μmol/L） significantly inhibited the proliferation of MCF7 cells after 24-hour or 48-hour treatment in a dose-dependent and time-dependent manner in the observation group as compared with that of the control group,and the highest inhibition was found at 10 μmol/L MLN8237 after 48-hour treatment（ all P〈 0. 05）. With the increasing concentrations of MLN8237,the percentage of cells in G2/M phase increased,the percentage of cells in G0/G1 and S decreased in the observation group as compared with that of the control group,and there was statistically significant difference between these two groups（ all P 〈0. 05）. Compared with the control group,with the increasing concentrations of MLN8237,the expression of p-Aurora A kinase and Bcl-2 decreased,the expression of Bax increased,the apoptosis rate increased and the highest apoptotic inhibition rate was found at 10 μmol/L MLN8237 after 24-hour treatment in the observation group（ all P 〈0. 05）. Conclusion MLN8237 inhibits the proliferation and induces the apoptosis of MCF7 cells.

关 键 词：乳腺癌 MLN8237 AURORA激酶抑制剂 细胞增殖 细胞凋亡 

分 类 号：R737.9[医药卫生—肿瘤]