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
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
WOS记录号WOS:000312043300020
项目编号81072597 ; 81130059 ; 2009CB930300 ; 7112089 ; BMU20110268 ; BMU20110263
资助机构NSFC ; National Basic Research Program of China (973 Program) ; Beijing NSF ; Ministry of Education
引用统计
被引频次:31[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/400002259/58223
专题北京大学药学院_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
推荐引用方式
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.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Tao, Xiao-Mei]的文章
[Wang, Jian-cheng]的文章
[Wang, Jia-bao]的文章
百度学术
百度学术中相似的文章
[Tao, Xiao-Mei]的文章
[Wang, Jian-cheng]的文章
[Wang, Jia-bao]的文章
必应学术
必应学术中相似的文章
[Tao, Xiao-Mei]的文章
[Wang, Jian-cheng]的文章
[Wang, Jia-bao]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。