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Naringenin Enhances the Anti-Tumor Effect of Doxorubicin Through Selectively Inhibiting the Activity of Multidrug Resistance-Associated Proteins but not P-glycoprotein
Zhang, Fa Yun1; Du, Gang Jun1,2; Zhang, Ling1; Zhang, Chun Ling1; Lu, Wan Liang3; Liang, Wei1,4
关键词Doxorubicin Drug Efflux Pumps Multidrug Resistance Naringenin
刊名PHARMACEUTICAL RESEARCH
2009-04-01
DOI10.1007/s11095-008-9793-y
26期:4页:914-925
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
资助者State Key Development Plan Project ; National Natural Science Foundation of China ; Chinese Academy of Sciences ; State Key Development Plan Project ; National Natural Science Foundation of China ; Chinese Academy of Sciences
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]MEDIATED TRANSPORT ; DRUG-RESISTANCE ; LUNG-CANCER ; PHASE-I ; (ABCG2)-MEDIATED TRANSPORT ; SUBSTRATE-SPECIFICITY ; GENE-EXPRESSION ; HUMAN GLIOMA ; CELL-LINES ; MRP GENE
英文摘要

Naringenin has shown paradoxical results to modulate the function of multidrug resistance-associated proteins (MRPs). The aim of this study is to interpret whether naringenin can reverse intrinsic and/or acquired resistance of cancer cells to chemotherapeutic agents.

The effects of naringenin on the uptake, retention and cytotoxicity of doxorubicin were investigated in A549, MCF-7, HepG2 and MCF-7/DOX cells. Cellular efflux pathways modulated by naringenin were assessed with their specific substrates and inhibitors. The improved antitumor activity of doxorubicin in combination with naringenin was also investigated in vivo.

The IC(50) values of doxorubicin in combination with naringenin in A549 and MCF-7 cells were approximately 2-fold lower than that of doxorubicin alone. The increased sensitivity to doxorubicin by naringenin in HepG2 and MCF-7/DOX cells was not observed. Naringenin increased the cellular doxorubicin accumulation through inhibiting doxorubicin efflux in the cells expressing MRPs but not P-gp. In contrast to doxorubicin alone, doxorubicin in combination with naringenin enhanced antitumor activity in vivo with low systemic toxicity.

Naringenin enhances antitumor effect of doxorubicin by selective modulating drug efflux pathways. Naringenin will be a useful adjunct to improve the effectiveness of chemotherapeutic agents in treatment of human cancers.

语种英语
所属项目编号2006CB705706 ; 2007CB935801 ; 90606019 ; 90713024 ; KSCX2-YW-R-21 ; KJCX2-YW-M02
资助者State Key Development Plan Project ; National Natural Science Foundation of China ; Chinese Academy of Sciences ; State Key Development Plan Project ; National Natural Science Foundation of China ; Chinese Academy of Sciences
WOS记录号WOS:000263799000017
引用统计
被引频次:30[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50242
专题北京大学药学院
作者单位1.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Prot & Peptide Pharmaceut Lab, Beijing 100101, Peoples R China
2.Henan Univ, Pharmaceut Coll, Dept Pharmacol, Kaifeng 475001, Peoples R China
3.Peking Univ, Sch Pharmaceut Sci, State Kay Lab Nat & Biomimet Drugs, Beijing 100083, Peoples R China
4.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China
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GB/T 7714
Zhang, Fa Yun,Du, Gang Jun,Zhang, Ling,et al. Naringenin Enhances the Anti-Tumor Effect of Doxorubicin Through Selectively Inhibiting the Activity of Multidrug Resistance-Associated Proteins but not P-glycoprotein[J]. PHARMACEUTICAL RESEARCH,2009,26(4):914-925.
APA Zhang, Fa Yun,Du, Gang Jun,Zhang, Ling,Zhang, Chun Ling,Lu, Wan Liang,&Liang, Wei.(2009).Naringenin Enhances the Anti-Tumor Effect of Doxorubicin Through Selectively Inhibiting the Activity of Multidrug Resistance-Associated Proteins but not P-glycoprotein.PHARMACEUTICAL RESEARCH,26(4),914-925.
MLA Zhang, Fa Yun,et al."Naringenin Enhances the Anti-Tumor Effect of Doxorubicin Through Selectively Inhibiting the Activity of Multidrug Resistance-Associated Proteins but not P-glycoprotein".PHARMACEUTICAL RESEARCH 26.4(2009):914-925.
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