胡桃醌衍生物MAM抑制人乳腺癌MDA-MB-231细胞增殖的体外研究  

Effects of 2-Methoxy-6-acetyl-7-methyljuglone on Proliferation of Human Breast Cancer MDA-MB-231 Cells in vitro

作　　者：林思思[1] 曾行[2] 罗丹[1] 陈彤丹 

机构地区：[1]浙江省人民医院,浙江杭州310014 [2]浙江大学附属第一医院,浙江杭州310003

出　　处：《肿瘤药学》2016年第1期39-43,共5页Anti-Tumor Pharmacy

摘　　要：目的探讨虎杖提取物2-甲氧基-6-乙酰基-7-甲基胡桃醌(2-Methoxy-6-acetyl-7-methyljuglone,MAM)对人乳腺癌细胞MAD-MB-231体外增殖的影响及可能机制。方法体外培养正常人肝细胞LO2、人乳腺癌MDA-MB-231和MDA-MB-468细胞,采用Cell Counting Kit-8(CCK8)法检测MAM对细胞增殖的影响,采用Hoechst33258染色检测MAM对MDA-MB-231细胞凋亡的影响,采用流式细胞术检测MAM对MDA-MB-231细胞周期的影响,western blot分析相关蛋白表达的变化。结果 MAM对人乳腺癌MDA-MB-231细胞生长有较强的抑制作用,呈剂量和时间依赖性。MAM作用24 h可诱导MDA-MB-231细胞发生典型的凋亡形态学改变,抑制MDA-MB-231细胞周期在G2/M期,同时显著下调细胞内Cdk1和Cyclin B1蛋白的表达、上调p-Cdk1(Thr14)的蛋白表达水平(P<0.05)。结论 MAM能够通过抑制Cdk1-Cyclin B1复合物的形成,使细胞周期阻滞在G2/M期,干扰细胞周期进程,从而抑制MDA-MB-231细胞的增殖。Objective To investigate the effects of 2-Methoxy-6-acetyl-7-methyljuglone （MAM） extracted from Polygonum cuspidatum （Hu Zhang） on the proliferation of human breast cancer MDA-MB-231 cells and its possible mechanisms. Method Human normal liver cell LO2 and human breast cancer cells （MDA-MB-231 and MDA-MB--468） were cultured in vitro. The effects of MAM on the growth in- hibition ratio of cells were evaluated by the Cell Counting Kit-8 （CCKS）. The effects of MAM on the apoptosis of MDA-MB-231 ceils were detected through morphological observation by Hoechst33258 staining. The effects of MAM on the cell cycle of MDA-MB-231 cells were detected through flow cytometric analysis （FCM）. The expressions of related proteins were analyzed by western blot. Results MAM signifi- cantly inhibited the growth and proliferation of MDA-MB-231 ceils in a dose- and time-dependent manner. Typical morphological change of apoptosis occurred in MDA-MB-231 cells when treated with MAM for 24 h, and increased cells were arrested in GJM phase. Western blot showed the expressions of Cdk 1 and CyclinB 1 were depressed, and protein expression of p-Cdk 1 （Thrl4） was up-regulated （P 〈 0.05）. Conclusion MAM inhibits the proliferation of MDA-MB-231 cells through GJM cell cycle arrest induction, which is mediated by depres- sion of Cdk 1-CyclinB 1 complex.

关 键 词：2-甲氧基-6-乙酰基-7-甲基胡桃醌 乳腺癌 增殖 CYCLIN B1 CDK1 

分 类 号：R737.9[医药卫生—肿瘤]