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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

颜亮, 昝嘉伟, 冯遵永, 马金珠, 徐蕾, 王毅

颜亮, 昝嘉伟, 冯遵永, 马金珠, 徐蕾, 王毅. 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[J]. 中国药科大学学报, 2018, 49(6): 718-824. DOI: 10.11665/j.issn.1000-5048.20180613
引用本文: 颜亮, 昝嘉伟, 冯遵永, 马金珠, 徐蕾, 王毅. 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[J]. 中国药科大学学报, 2018, 49(6): 718-824. DOI: 10.11665/j.issn.1000-5048.20180613
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YAN Liang, ZAN Jiawei, FENG Zunyong, MA Jinzhu, XU Lei, WANG Yi. Dipyridyl pyrrolidine inhibits MDA-MB231 breast cancer cell cycle by inhibiting AKT-mTOR[J]. Journal of China Pharmaceutical University, 2018, 49(6): 718-824. DOI: 10.11665/j.issn.1000-5048.20180613
Citation: YAN Liang, ZAN Jiawei, FENG Zunyong, MA Jinzhu, XU Lei, WANG Yi. Dipyridyl pyrrolidine inhibits MDA-MB231 breast cancer cell cycle by inhibiting AKT-mTOR[J]. Journal of China Pharmaceutical University, 2018, 49(6): 718-824. DOI: 10.11665/j.issn.1000-5048.20180613
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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

  • 1.

    皖南医学院活性生物大分子安徽省重点实验室

  • 2.

    安徽师范大学生命科学学院

  • 3.

    南京大学化工学院江苏省先进有机材料重点实验室

基金项目: 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)

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

摘要

    摘要
  • 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MDA-MB231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/EdU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/mL剂量依赖性抑制MDA-MB231细胞活力，下调EdU阳性细胞数量，增加G1期并减少S/G2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。
    Abstract: To investigate the induction of cell cycle arrest of human breast cancer MDA-MB231 cells by Di-indolyl pyrrolidine(DIPRD), a pyrrolidine-derived spirooxindoles compounds. The cytotoxic effect of DIPRD on MDA-MB231 cells was detected by CCK-8 method. The cell cycle arrest of MDA-MB231 cells 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-MB231 cells by downregulating the number of EdU-positive cells, increase G1 phase and reduce cell number in S/G2 phase, down-regulated the p-AKT(Ser473), p-mTOR, p-p53, cyclin D1, CDK4, and the upregulated the p-AKT(Thr308), p-MDM2 and Cleaved-PARP levels were detected in a dose-dependent manner at 12. 5, 25, and 50 mg/mL. DIPRD may play a role in cell cycle arrest through AKT signaling pathway and induce cell apoptosis.
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  • 刊出日期:  2018-12-24

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