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首页> 外文期刊>RSC Advances >Study on mechanism of elemene reversing tumor multidrug resistance based on luminescence pharmacokinetics in tumor cellsin vitroandin vivo
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Study on mechanism of elemene reversing tumor multidrug resistance based on luminescence pharmacokinetics in tumor cellsin vitroandin vivo

机译：基于肿瘤细胞培养基体内的发光药代动力学的榄烯逆转肿瘤多药耐药机制研究

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摘要

While elemene (ELE) can reverse tumor multidrug resistance (MDR), the mechanisms for ELE reversing MDR remain unclear. Numerous studies have suggested that the efflux functionality of ATP-binding cassette (ABC) transporters, not their quantity, is more relevant to tumor MDR. However, no appropriate methods exist for real-time detection of the intracellular drug efflux caused by ABC transportersin vitro, especiallyin vivo, which hinders the examination of MDR reversal mechanisms. This study directly investigates the correlation between efflux functionality of ABC transporters and MDR reversalviaELE, usingd-luciferin potassium salt (d-luc) as the chemotherapeutic substitute to study the intracellular drug efflux. Here, a luciferase reporter assay system combined with bioluminescence imaging confirmed that the efflux ofd-luc from MCF-7/DOX(Fluc)cellsin vitroandin vivowas significantly reduced by ELE and when combined with Doxorubicin (DOX), ELE showed a synergistically anti-tumor effectin vitroandin vivo. Additionally, the luminescence pharmacokinetics ofd-luc in MCF-7/DOX(Fluc)cells and pharmacodynamics of the combined ELE and DOXin vivoshowed a great correlation, implying thatd-luc might be used as a probe to study ABC transporters-mediated efflux in order to explore mechanisms of traditional Chinese medicines reversing MDR.
机译：虽然Elemene（ELE）可以逆转肿瘤多药耐药性（MDR），但ELE逆转MDR的机制仍不清楚。许多研究表明，ATP结合盒（ABC）转运蛋白，而不是它们的数量的流出函数与肿瘤MDR更相关。然而，没有适当的方法，用于实时检测由ABC转运蛋白体外引起的细胞内药物流出，尤其是体内，阻碍了MDR逆转机制的检查。本研究直接研究了ABC转运蛋白和MDR Reversalviaele的渗透功能与MDRUC磷盐（D-LUC）作为化学治疗替代物的相关性，以研究细胞内药物流出。在这里，荧光素酶报道基因测定系统与生物发光成像组合证实，从MCF-7 / DOX（Fluc的）流出OFD-luc的cellsin vitroandin vivowas通过ELE显著减少，并且当与多柔比星（DOX）相结合，ELE呈协同抗肿瘤有效vitroandin体内。另外，MCF-7 / DOX（FLUC）细胞（组合ELE和Doxin的药效学）的发光药代动力学和含量的药效学强，暗示暗示That-Luc作为探针，以研究ABC转运蛋白介导的流出探讨逆转MDR的中药机制。

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  • 来源
    《RSC Advances》 |2020年第57期|共10页
  • 作者

    Chen Liying; Chen Zhi; Zheng Shuang; Fan Luhui; Zhu Lixin; Yu Jiandong; Tang Chaoyuan; Liu Qi; Xiong Yang;

  • 作者单位

    Zhejiang Chinese Med Univ Dept Pharmaceut Sci Coll Pharmaceut Sci Hangzhou 311400 Zhejiang Peoples R China;

    Zhejiang Chinese Med Univ Dept Pharmaceut Sci Coll Pharmaceut Sci Hangzhou 311400 Zhejiang Peoples R China;

    Zhejiang Chinese Med Univ Dept Pharmaceut Sci Coll Pharmaceut Sci Hangzhou 311400 Zhejiang Peoples R China;

    Zhejiang Chinese Med Univ Dept Pharmaceut Sci Coll Pharmaceut Sci Hangzhou 311400 Zhejiang Peoples R China;

    Zhejiang Chinese Med Univ Dept Pharmaceut Sci Coll Pharmaceut Sci Hangzhou 311400 Zhejiang Peoples R China;

    Zhejiang Chinese Med Univ Dept Pharmaceut Sci Coll Pharmaceut Sci Hangzhou 311400 Zhejiang Peoples R China;

    Zhejiang Chinese Med Univ Dept Pharmaceut Sci Coll Pharmaceut Sci Hangzhou 311400 Zhejiang Peoples R China;

    Johns Hopkins Univ Dept Dermatol Sch Med Baltimore MD 21231 USA;

    Zhejiang Chinese Med Univ Dept Pharmaceut Sci Coll Pharmaceut Sci Hangzhou 311400 Zhejiang Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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