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  • ISSN 1006-3080
  • CN 31-1691/TQ

顺苯磺酸阿曲库铵(51w89)作为CD73抑制剂的发现及评价

刘永杰 汤姜杨 朱丽丽 李洪林

刘永杰, 汤姜杨, 朱丽丽, 李洪林. 顺苯磺酸阿曲库铵(51w89)作为CD73抑制剂的发现及评价[J]. 华东理工大学学报(自然科学版). doi: 10.14135/j.cnki.1006-3080.20220122003
引用本文: 刘永杰, 汤姜杨, 朱丽丽, 李洪林. 顺苯磺酸阿曲库铵(51w89)作为CD73抑制剂的发现及评价[J]. 华东理工大学学报(自然科学版). doi: 10.14135/j.cnki.1006-3080.20220122003
LIU Yongjie, TANG Jiangyang, ZHU Lili, LI Honglin. Discovery and Evaluation of Cisatracurium Besylate (51w89) As An Inhibitor of CD73[J]. Journal of East China University of Science and Technology. doi: 10.14135/j.cnki.1006-3080.20220122003
Citation: LIU Yongjie, TANG Jiangyang, ZHU Lili, LI Honglin. Discovery and Evaluation of Cisatracurium Besylate (51w89) As An Inhibitor of CD73[J]. Journal of East China University of Science and Technology. doi: 10.14135/j.cnki.1006-3080.20220122003

顺苯磺酸阿曲库铵(51w89)作为CD73抑制剂的发现及评价

doi: 10.14135/j.cnki.1006-3080.20220122003
基金项目: 国家杰出青年科学基金(81825020)
详细信息
    作者简介:

    刘永杰(1993—),男,山东菏泽,硕士,主要研究方向:药物筛选及评价。E-mail:18766136551@163.com

    通讯作者:

    朱丽丽, E-mail:zhulfl@ecust.edu.cn

  • 中图分类号: R915

Discovery and Evaluation of Cisatracurium Besylate (51w89) As An Inhibitor of CD73

  • 摘要: CD73是一个新兴的肿瘤治疗潜在靶点,与肿瘤的发生、发展、转移及不良预后密切相关。在本研究中,我们通过筛选发现顺苯磺酸阿曲库铵(51w89)可以抑制CD73的酶活性,其在分子水平的IC50为13.30 μmol/L;通过表面等离子共振实验测得51w89与CD73蛋白的结合亲和力KD为20.45 μmol/L;在高表达CD73的人乳腺癌细胞MDA-MB-231中测得51w89抑制细胞中CD73的酶活性IC50为17.70 μmol/L。进一步的研究结果显示,51w89可抑制MDA-MB-231细胞的迁移能力;并且51w89限制AMP对CD8+T细胞分泌IFN-γ的抑制作用。通过以上一系列研究表明,51w89可作为CD73潜在抑制剂用于后续的抗肿瘤研究。

     

  • 图  1  51w89抑制重组蛋白CD73的酶活性

    Figure  1.  Results for the inhibition activity of 51w89 against recombinant CD73

    (a) The primarily screening results against CD73 (red point: 51w89); (b) The IC50 result of 51w89 against recombinant CD73

    图  2  51w89与重组CD73蛋白结合的SPR图

    Figure  2.  SPR results for the binding affinity between 51w89 and CD73

    图  3  51w89抑制人乳腺癌细胞MDA-MB-231中CD73的酶活性

    Figure  3.  Results for the inhibition activity of 51w89 against CD73 in MDA-MB-231 cells

    (a) Western blot analysis for the expression of CD73 in different cells; (b) The IC50 result of 51w89 against CD73 in MDA-MB-231 cells

    图  4  51w89或siRNA下调CD73表达可抑制MDA-MB-231细胞的迁移能力

    Figure  4.  Inhibitory effects of 51W89 or siRNA CD73 on the migration of MDA-MB-231 cells by transwell tests

    (a) The effect of CD73 siRNA on CD73 expression in MB-MDA-231 cells.; (b) Effects of 51W89 or siRNA CD73 on the migration of MDA-MB-231 cells

    图  5  划痕实验表明51w89抑制MDA-MB-231细胞迁移

    Figure  5.  Inhibitory effects of 51w89 on the migration of MDA-MB-231 cells by scratch tests

    图  6  ELISA法测定CD8+T细胞分泌IFN-γ的水平

    Figure  6.  Measurements of IFN-γ secretion in CD8+T cells by ELISA

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出版历程
  • 收稿日期:  2022-01-22
  • 网络出版日期:  2022-04-12

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