IR@PKUHSC  > 北京大学药学院  > 药剂学系
学科主题药学
Enhanced anticancer activity of gemcitabine coupling with conjugated linoleic acid against human breast cancer in vitro and in vivo
Tao, Xiao-Mei2; Wang, Jian-cheng1; Wang, Jia-bao2; Feng, Qiang; Gao, Shan-yun; Zhang, Liang-Ren; Zhang, Qiang
关键词Gemcitabine Conjugated linoleic acid Prodrug Anticancer activity
刊名EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
2012-10-01
DOI10.1016/j.ejpb.2012.06.007
82期:2页:401-409
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
资助者NSFC ; National Basic Research Program of China (973 Program) ; Beijing NSF ; Ministry of Education ; NSFC ; National Basic Research Program of China (973 Program) ; Beijing NSF ; Ministry of Education
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]EQUILIBRATIVE NUCLEOSIDE TRANSPORTER-1 ; DRUG-RESISTANCE ; CELL LINES ; CYTOTOXICITY ; CHEMOTHERAPY ; SURVIVAL ; THERAPY ; ISOMERS ; PATHWAY ; ABSENCE
英文摘要

Gemcitabine (GEM) is a nucleoside analog agent against a wide variety of tumors. To overcome its limitation of rapid metabolism in vivo that results in short circulation time and poor antitumor efficacy, a novel prodrug (CLA-GEM conjugate) has been developed through the covalent coupling of conjugated linoleic acid (CLA) to N-4-amino group of GEM. The chemical structure of CLA-GEM conjugate was identified by NMR, FUR and other methods. From in vitro tests, it was demonstrated that the linkage with CLA increased the plasma stability of GEM as well as the antitumor activity against human breast tumor cells (MCF-7). Importantly, it also altered the transport pattern of GEM across cell membrane (MCF-7 and MDA-MB-231), evidenced by the little effect of nucleoside transporter inhibitors (NBMPR and dipyridamole) on the IC50 values of CLA-GEM, instead of the great effect on that of unmodified GEM. In vivo pharmacokinetic study showed that the CLA-GEM conjugate had a longer plasma half-life and a higher bioavailability compared to that of unmodified GEM. Significant stronger antitumor activity was observed in the nude mice xenografted MCF-7 breast tumor after treated with CLA-GEM than that of unmodified GEM, while no significant body weight loss was found in all treatments. In conclusion, the novel CIA-GEM conjugate prepared in this study would be a promising prodrug of gemcitabine for future clinical use. (C) 2012 Elsevier B.V. All rights reserved.

语种英语
所属项目编号81072597 ; 81130059 ; 2009CB930300 ; 7112089 ; BMU20110268 ; BMU20110263
资助者NSFC ; National Basic Research Program of China (973 Program) ; Beijing NSF ; Ministry of Education ; NSFC ; National Basic Research Program of China (973 Program) ; Beijing NSF ; Ministry of Education
WOS记录号WOS:000312043300020
Citation statistics
Cited Times:31[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58223
Collection北京大学药学院_药剂学系
作者单位1.Peking Univ, Dept Pharmaceut, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.ShenYang Pharmaceut Univ, Dept Pharmaceut, Shenyang, Peoples R China
Recommended Citation
GB/T 7714
Tao, Xiao-Mei,Wang, Jian-cheng,Wang, Jia-bao,et al. Enhanced anticancer activity of gemcitabine coupling with conjugated linoleic acid against human breast cancer in vitro and in vivo[J]. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS,2012,82(2):401-409.
APA Tao, Xiao-Mei.,Wang, Jian-cheng.,Wang, Jia-bao.,Feng, Qiang.,Gao, Shan-yun.,...&Zhang, Qiang.(2012).Enhanced anticancer activity of gemcitabine coupling with conjugated linoleic acid against human breast cancer in vitro and in vivo.EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS,82(2),401-409.
MLA Tao, Xiao-Mei,et al."Enhanced anticancer activity of gemcitabine coupling with conjugated linoleic acid against human breast cancer in vitro and in vivo".EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS 82.2(2012):401-409.
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