二吲哚吡啶基吡咯烷通过抑制AKT-mTOR阻滞MDA-MB231乳腺癌细胞周期  

Dipyridyl pyrrolidine inhibits MDA-MB231 breast cancer cell cycle by inhibiting AKT-mTOR

作　　者：颜亮[1] 昝嘉伟 冯遵永[1] 马金珠[1] 徐蕾[1] 王毅[3] YAN Liang;ZAN Jiawei;FENG Zunyong;MA Jinzhu;XU Lei;WANG Yi(Provincial Key Laboratory of Biological Macro-molecules Research,Wannan Medical College,Wuhu 241002;School of Life Sciences,Anhui Normal University,Wuhu 241002;Jiangsu Key Laboratory of Advanced Organic Materials,School of Chemistry & Chemical Engineering ,Nanjing University,Nanjing 210023,China)

机构地区：[1]皖南医学院活性生物大分子安徽省重点实验室,芜湖241002 [2]安徽师范大学生命科学学院,芜湖241002 [3]南京大学化工学院江苏省先进有机材料重点实验室,南京210023

出　　处：《中国药科大学学报》2018年第6期718-724,共7页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.21472082;No.81802651);安徽省教育厅自然科学研究重点项目(No.2017KJA256)~~

摘　　要：探索吡咯烷衍生物的螺旋吲哚化合物二吲哚吡啶基吡咯烷(Di-indolyl pyrrolidine,DIPRD)对人乳腺癌MDAMB231细胞周期的阻滞作用。使用CCK-8法检测DIPRD对MDA-MB231细胞的毒性剂量;使用DAPI/Ed U双染法检测MDA-MB231细胞周期阻滞作用;使用Western blot检测信号通路蛋白AKT、mTOR和凋亡相关蛋白p53、MDM2的磷酸化水平以及DNA修复酶PARP的水平。DIPRD在12. 5、25、50 mg/m L剂量依赖性抑制MDA-MB231细胞活力,下调EdU阳性细胞数量,增加G_1期并减少S/G_2期细胞数量,下调p-AKT(Ser473)、p-mTOR、p-p53、cyclin D1和CDK4水平并上调p-AKT(Thr308),p-MDM2及Cleaved-PARP水平。DIPRD可能通过AKT信号通路发挥周期阻滞作用。To investigate the induction of cell cycle arrest of human breast cancer MDA-MB231cells by Di-indolyl pyrrolidine(DIPRD),a pyrrolidine-derived spirooxindoles compounds.The cytotoxic effect of DIPRD on MDA-MB231cells was detected by CCK-8method.The cell cycle arrest of MDA-MB231cells was detected by DAPI/EdU double-staining.Phosphorylation levels of AKT,mTOR,apoptosis-related proteins p53,MDM2,and DNA repair enzyme PARP levels were detected by Western blot.DIPRD inhibited the viability of MDA-MB231cells by downregulating the number of EdU-positive cells,increase G1phase and reduce cell number in S/G2phase,down-regulated the p-AKT(Ser473),p-mTOR,p-p53,cyclin D1,CDK4,and the upregulated the p-AKT(Thr308),p-MDM2and Cleaved-PARP levels were detected in a dose-dependent manner at12.5,25,and50mg/mL.DIPRD may play a role in cell cycle arrest through AKT signaling pathway and induce cell apoptosis.

关 键 词：二吲哚吡啶基吡咯烷 乳腺癌 MDA-MB231 细胞周期 

分 类 号：R965[医药卫生—药理学]