Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma

doi:10.2147/IJN.S115956

科研成果详情

题名	Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma
作者	Zhang, Lu 1,2,3; Lu, Jiafei 3; Qiu, Liyan 1
发表日期	2016-12-31
发表期刊	INTERNATIONAL JOURNAL OF NANOMEDICINE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	multidrug resistance P-glycoprotein micelle doxorubicin zebrafish
其他关键词	OVERCOME MULTIDRUG-RESISTANCE ; PLURONIC BLOCK-COPOLYMERS ; P-GLYCOPROTEIN EXPRESSION ; BETA-CYCLODEXTRIN ; CANCER-CELLS ; DOXORUBICIN DELIVERY ; ANTITUMOR EFFICACY ; POLYMERIC MICELLES ; ENERGY DEPLETION ; DOWN-REGULATION
摘要	P-glycoprotein (P-gp) overexpression has become the most common cause of occurrence of multidrug resistance in clinical settings. We aimed to construct a micellar polymer carrier to sensitize drug-resistant tumors to doxorubicin (DOX). This A-B-C-type amphiphilic copolymer was prepared by the sequential linkage of beta-cyclodextrin, hydrophobic poly(D, L-lactide), and hydrophilic poly(ethylene glycol). Upon incubation of the DOX-loaded micelles with DOX-resistant human breast carcinoma MCF-7/ADR cells, significantly enhanced cytotoxicity and apoptosis were achieved. A series of studies on the action mechanism showed that the polymer components such as beta-cyclodextrin, hydrophobic poly(D, L-lactide) segment, and poly(ethylene glycol) coordinatively contributed to the improved intracellular ATP depletion and ATPase activity, increased intracellular uptake of P-gp substrates via competitive binding to P-gp, and decreased P-gp expression in MCF-7/ADR cells. More interestingly, a similar phenomenon was observed in the zebrafish xenograft model, resulting in similar to 64% inhibition of MCF-7/ADR tumor growth. These results implied that the polymeric micelles displayed great potentials as P-gp modulators to reverse DOX resistance in MCF-7/ADR breast carcinoma.
资助项目	National Natural Science Funds for Excellent Young Scholar [81222047]; National Natural Science FundsNational Natural Science Foundation of China (NSFC) [81473173]
出版者	DOVE MEDICAL PRESS LTD
出版地	ALBANY
ISSN	1178-2013
EISSN	1178-2013
卷号	11 页码:5205-5220
DOI	10.2147/IJN.S115956
页数	16
WOS类目	Nanoscience & Nanotechnology ; Pharmacology & Pharmacy
WOS研究方向	Science & Technology - Other Topics ; Pharmacology & Pharmacy
WOS记录号	WOS:000385046600001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	27785023
PMC记录号	PMC5066852
SCOPUSEID	2-s2.0-84991577868
通讯作者地址	[Qiu, Liyan]Ministry of Education (MOE),Key Laboratory of Macromolecular Synthesis and Functionalization,Department of Polymer Science and Engineering,Zhejiang University,38 Zheda Road,Hangzhou,310027,China
Scopus学科分类	Biophysics;Bioengineering;Biomaterials;Pharmaceutical Science;Drug Discovery;Organic Chemistry
引用统计	被引频次：6[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/4290
专题	附属第一医院_药物临床试验机构办公室
通讯作者	Qiu, Liyan
作者单位	1.Ministry of Education (MOE),Key Laboratory of Macromolecular Synthesis and Functionalization,Department of Polymer Science and Engineering,Zhejiang University,Hangzhou,China; 2.Drug Clinical Trial Office,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 3.College of Pharmaceutical Sciences,Zhejiang University,Hangzhou,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
推荐引用方式 GB/T 7714	Zhang, Lu,Lu, Jiafei,Qiu, Liyan. Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma[J]. INTERNATIONAL JOURNAL OF NANOMEDICINE,2016,11:5205-5220.
APA	Zhang, Lu, Lu, Jiafei, & Qiu, Liyan. (2016). Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma. INTERNATIONAL JOURNAL OF NANOMEDICINE, 11, 5205-5220.
MLA	Zhang, Lu,et al."Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma".INTERNATIONAL JOURNAL OF NANOMEDICINE 11(2016):5205-5220.