SIOC OpenIR  > 生命有机化学国家重点实验室
Gefitinib Analogue V1801 Induces Apoptosis of T790M EGFR-Harboring Lung Cancer Cells by Up-Regulation ofthe BH-3 Only Protein Noxa
其他题名吉非替尼类似物V1801通过增量调节BH-3域蛋白Noxa诱导表皮生长因子受体 T790M包裹的肺癌细胞的凋亡
Zhang B(张波); Jiao J(焦姣); LIU YING; Guo LX(郭良霞); ZHOU BO; Li GQ(李纲琴); Yao ZJ(姚祝军); Zhou GB(周光飚)
2012
发表期刊PLoS One
ISSN1932-6203
卷号7期号:11页码:e48748
摘要Treatment of non-small cell lung cancer (NSCLC) with drugs targeting the epidermal growth factor receptor (EGFR), e. g., gefitinib and erlotinib, will eventually fail because of the development of secondary mutations such as T790M in EGFR. Strategies to overcome this resistance are therefore an urgent need. In this study, we synthesized a dozen of novel gefitinib analogues and evaluated their effects on L858R/T790M-EGFR harboring NSCLC cells, and reported that one of these gefitinib mimetics, N-(2-bromo-5-(trifluoromethyl) phenyl)-6-methoxy-7-(3-(piperidin-1-yl)propoxy)quinazolin-4-amine (hereafter, V1801), triggered apoptosis of the NSCLC cells and overcame gefitinib-resistance in mice inoculated with NCI-H1975 cells. Though V1801 only moderately inhibited EGFR kinase activity, it markedly induced the expression of the BH3-only protein Noxa, and Noxa silencing significantly reduced V1801-induced apoptosis of NCI-H1975 cells. It is showed that V1801 interfered with the expression of the transcription factor c-Myc and the extracellular signal regulated kinase (Erk) pathway. V1801 in combination with proteasome inhibitor bortezomib exerted enhanced cytotoxicity in NCI-H1975 cells possibly due to potentiated induction of Noxa expression. These data indicate that gefinitib analogues with weak EGFR inhibitory activity may overcome drug-resistance via activation of BH-3 only pro-apoptotic proteins, and V1801 may have therapeutic potentials for NSCLC.
学科领域生命有机化学
部门归属中科院动物研究所; 中科院上海有机化学研究所; 中国科学院大学; 清华大学深圳研究生院
URL查看原文
收录类别SCI
语种英语
文献类型期刊论文
条目标识符http://ir.sioc.ac.cn/handle/331003/28513
专题生命有机化学国家重点实验室
通讯作者Yao ZJ(姚祝军); Zhou GB(周光飚)
推荐引用方式
GB/T 7714
Zhang B,Jiao J,LIU YING,et al. Gefitinib Analogue V1801 Induces Apoptosis of T790M EGFR-Harboring Lung Cancer Cells by Up-Regulation ofthe BH-3 Only Protein Noxa[J]. PLoS One,2012,7(11):e48748.
APA 张波.,焦姣.,LIU YING.,郭良霞.,ZHOU BO.,...&周光飚.(2012).Gefitinib Analogue V1801 Induces Apoptosis of T790M EGFR-Harboring Lung Cancer Cells by Up-Regulation ofthe BH-3 Only Protein Noxa.PLoS One,7(11),e48748.
MLA 张波,et al."Gefitinib Analogue V1801 Induces Apoptosis of T790M EGFR-Harboring Lung Cancer Cells by Up-Regulation ofthe BH-3 Only Protein Noxa".PLoS One 7.11(2012):e48748.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
2012072.pdf(1770KB) 开放获取--请求全文
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
[张波]的文章
[焦姣]的文章
[LIU YING]的文章
百度学术
百度学术中相似的文章
[张波]的文章
[焦姣]的文章
[LIU YING]的文章
必应学术
必应学术中相似的文章
[张波]的文章
[焦姣]的文章
[LIU YING]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。