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  • ISSN 1006-3080
  • CN 31-1691/TQ

槲皮苷铜配合物作为P-糖蛋白抑制剂的研究

邓燕 刘慧 张飞旭 吴侠 郑静 张井岩

邓燕, 刘慧, 张飞旭, 吴侠, 郑静, 张井岩. 槲皮苷铜配合物作为P-糖蛋白抑制剂的研究[J]. 华东理工大学学报(自然科学版), 2020, 46(5): 680-687. doi: 10.14135/j.cnki.1006-3080.20190601001
引用本文: 邓燕, 刘慧, 张飞旭, 吴侠, 郑静, 张井岩. 槲皮苷铜配合物作为P-糖蛋白抑制剂的研究[J]. 华东理工大学学报(自然科学版), 2020, 46(5): 680-687. doi: 10.14135/j.cnki.1006-3080.20190601001
DENG Yan, LIU Hui, ZHANG Feixu, WU Xia, ZHENG Jing, ZHANG Jingyan. Study on Cu-Quercitrin as a Novel P-gp Inhibitor[J]. Journal of East China University of Science and Technology, 2020, 46(5): 680-687. doi: 10.14135/j.cnki.1006-3080.20190601001
Citation: DENG Yan, LIU Hui, ZHANG Feixu, WU Xia, ZHENG Jing, ZHANG Jingyan. Study on Cu-Quercitrin as a Novel P-gp Inhibitor[J]. Journal of East China University of Science and Technology, 2020, 46(5): 680-687. doi: 10.14135/j.cnki.1006-3080.20190601001

槲皮苷铜配合物作为P-糖蛋白抑制剂的研究

doi: 10.14135/j.cnki.1006-3080.20190601001
基金项目: 国家自然科学基金(21671065);中央高校基本科研业务费专项资金
详细信息
    作者简介:

    邓燕:邓 燕(1991-),女,山东人,硕士生,从事P-糖蛋白抑制剂的研究。E-mail:dengyanxinlang@sina.com

    通讯作者:

    郑 静,E-mail:zhengjing@ecust.edu.cn

  • 中图分类号: R914; R965

Study on Cu-Quercitrin as a Novel P-gp Inhibitor

  • 摘要: P-糖蛋白(P-gp)是细胞产生多药耐药的主要原因之一,寻找有效的P-gp抑制剂是逆转P-gp介导的细胞多药耐药性的重要方法之一。以具有微弱P-gp抑制活性的天然槲皮苷为配体,合成了槲皮苷铜(Cu-Quercitrin)和槲皮苷锌(Zn-Quercitrin)配合物。结果表明,Cu-Quercitrin能提高P-gp的底物罗丹明123(Rh123)和抗癌药物阿霉素(DOX)在耐药细胞中的累积,同时增强了DOX的细胞毒性,表明Cu-Quercitrin可以抑制P-gp的活性,且优于常见的抑制剂维拉帕米;Cu-Quercitrin对P-gp蛋白水平表达并没有影响,只是减少了细胞中腺苷三磷酸(ATP)的含量。这一研究结果表明结构多样、配体丰富的金属配合物有望成为有效的P-gp抑制剂。

     

  • 图  1  Cu-Quercitrin、Zn-Quercitrin和Quercitrin的紫外吸收光谱(a),红外光谱(b);Cu-Quercitrin(c)和Zn-Quercitrin(d)的化学结构

    Figure  1.  UV-vis spectra (a), FT-IR spectra (b) of Cu-Quercitrin, Zn-Quercitrin and Quercitrin; Chemical structures of Cu-Quercitrin (c) and Zn-Quercitrin (d)

    图  2  Rh123在MCF-7/ADR细胞内的积累

    Figure  2.  Accumulation of Rh123 in MCF-7/ADR cells

    图  3  DOX在MCF-7/ADR细胞内的积累

    Figure  3.  Accumulation of DOX in MCF-7/ADR cells

    图  4  DOX和Rh123在MCF-7细胞内的积累

    Figure  4.  Accumulation of DOX and Rh123 in MCF-7 cells

    图  5  Cu-Quercitrin对DOX在MCF-7/ADR细胞中细胞毒性的影响

    Figure  5.  Effect of Cu-Quercitrin on cytotoxicity of DOX in MCF-7/ADR cells

    图  6  Cu-Quercitrin对P-gp在MCF-7/ADR细胞中表达的影响  

    Figure  6.  Effect of Cu-Quercitrin on the expression of P-gp in MCF-7/ADR cells

    图  7  Cu-Quercitrin对MCF-7/ADR细胞(a)和MCF-7细胞(b)中ATP含量的影响

    Figure  7.  Effect of Cu-Quercitrin on the ATP content in MCF-7/ADR (a) and MCF-7 (b) cells

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出版历程
  • 收稿日期:  2019-06-01
  • 网络出版日期:  2020-07-01
  • 刊出日期:  2020-10-30

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