北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学药学院  > 期刊论文
学科主题: 药学
题名:
Pegylated Phosphotidylethanolamine Inhibiting P-Glycoprotein Expression and Enhancing Retention of Doxorubicin in MCF7/ADR Cells
作者: Wang, Jing1; Qu, Hui1; Jin, Lingtao1; Zeng, Wenfeng1; Qin, Lei1; Zhang, Fayun1; Wei, Xiuli1; Lu, Wanliang2; Zhang, Chunling1; Liang, Wei1
关键词: P-glycoprotein ; PEG-PE ; Polymeric drug carrier ; Micelle ; multidrug resistance ; MDR-1 siRNA ; doxorubicin ; Cancer chemotherapy
刊名: JOURNAL OF PHARMACEUTICAL SCIENCES
发表日期: 2011-06-01
DOI: 10.1002/jps.22461
卷: 100, 期:6, 页:2267-2277
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Medicinal ; Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy ; Chemistry
关键词[WOS]: SENSITIVE POLYMERIC MICELLES ; TUMOR VASCULAR-PERMEABILITY ; FATTY-ACID DIESTERS ; MULTIDRUG-RESISTANCE ; MOLECULAR-MECHANISMS ; CANCER-CELLS ; DRUG ; DELIVERY ; GENE ; TRANSPORTERS
英文摘要:

The failure of the clinical treatment of cancer patients is often attributed to drug resistance of the tumor to chemotherapeutic agents. P-glycoprotein (P-gp) contributes to drug resistance via adenosine 5′-triphosphate (ATP)-dependent drug efflux pumps and is widely expressed in many human cancers. Up to date, a few of nanomaterials have shown the effects on P-gp function by different ways. To study the mechanism of the increased cytotoxicity of doxorubicin (DOX) by pegylated phosphotidylethanolamine (PEG-PE) in drug-resistant cancer cells, a series of in vitro cell assays were performed, including identification of P-gp function, quantitative studies on uptake and efflux of DOX, inhibitory effects of blank PEG-PE micelles on mRNA and protein levels of P-gp, and intracellular ATP content alteration. Finally, combining MDR-1 RNA interference (siRNA) with DOX encapsulated in PEG-PE micelles (M-DOX) to improve cytotoxicity of DOX was also studied. M-DOX showed fivefold lower the concentration that caused 50% killing tumor cellthan that of free DOX in the P-gp-overexpressing MCF-7 breast cancer (MCF-7/ADR) cells. M-DOX enhanced the cellular uptake and retention of DOX in MCF-7/ADR cells. PEG-PE block molecules can inhibit P-gp expression through downregulating MDR-1 gene. Cytotoxicity of M-DOX was further improved by knocking down the MDR-1 gene using siRNA in the multidrug-resistant cells. We conclude that the increased cytotoxicity of DOX encapsulated in PEG-PE micelle is due to the reduced P-gp expression by PEG-PE block molecules, and accordingly enhancing the cellular accumulation of DOX. To overcome drug resistance of tumor cells, the combination of nanotechnology and biotechnology could be an effective strategy such as PEG-PE formed micelles and siRNA. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2267-2277, 2011

语种: 英语
所属项目编号: 2006CB933305 ; 2007CB935801 ; 90606019 ; 30901869 ; 2009ZX09501-025 ; 2008DFA01510
项目资助者: State Key Development Plan Project ; National Nature Sciences Foundation of China ; National Science and Technology Special Project of Major New Drugs Creation ; China-Finland Inter-Governmental S&amp ; T Cooperation Project
WOS记录号: WOS:000289442200023
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51017
Appears in Collections:北京大学药学院_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Chinese Acad Sci, Natl Lab Biomacromol, Inst Biophys, Prot & Peptide Pharmaceut Lab, Beijing 100101, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Beijing 100083, Peoples R China

Recommended Citation:
Wang, Jing,Qu, Hui,Jin, Lingtao,et al. Pegylated Phosphotidylethanolamine Inhibiting P-Glycoprotein Expression and Enhancing Retention of Doxorubicin in MCF7/ADR Cells[J]. JOURNAL OF PHARMACEUTICAL SCIENCES,2011,100(6):2267-2277.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Wang, Jing]'s Articles
[Qu, Hui]'s Articles
[Jin, Lingtao]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Wang, Jing]‘s Articles
[Qu, Hui]‘s Articles
[Jin, Lingtao]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace