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学科主题: 药学
题名:
Naringenin Enhances the Anti-Tumor Effect of Doxorubicin Through Selectively Inhibiting the Activity of Multidrug Resistance-Associated Proteins but not P-glycoprotein
作者: 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
发表日期: 2009-04-01
DOI: 10.1007/s11095-008-9793-y
卷: 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
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
项目资助者: State Key Development Plan Project ; National Natural Science Foundation of China ; Chinese Academy of Sciences
WOS记录号: WOS:000263799000017
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50242
Appears in Collections:北京大学药学院_期刊论文

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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

Recommended Citation:
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.
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