中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 分子影像中心（筹）
Triptolide Inhibits the AR Signaling Pathway to Suppress the Proliferation of Enzalutamide Resistant Prostate Cancer Cells

文献类型：期刊论文

作者Han, Yangyang2; Huang, Weiwei2; Liu, Jiakuan3,4; Liu, Dandan5,6; Cui, Yangyan3,4; Huang, Ruimin5,6; Yan, Jun3,4; Lei, Ming1,2
刊名THERANOSTICS
出版日期2017
卷号7期号:7页码:1914-1927
关键词Triptolide Enzalutamide Castration-resistant prostate cancer Androgen receptor Phosphorylation
ISSN号1838-7640
DOI10.7150/thno.17852
文献子类Article
英文摘要Enzalutamide is a second-generation androgen receptor (AR) antagonist for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Unfortunately, AR dysfunction means that resistance to enzalutamide will eventually develop. Thus, novel agents are urgently needed to treat this devastating disease. Triptolide (TPL), a key active compound extracted from the Chinese herb Thunder God Vine (Tripterygium wilfordii Hook F.), possesses anti-cancer activity in human prostate cancer cells. However, the effects of TPL against CRPC cells and the underlying mechanism of any such effect are unknown. In this study, we found that TPL at low dose inhibits the transactivation activity of both full-length and truncated AR without changing their protein levels. Interestingly, TPL inhibits phosphorylation of AR and its CRPC-associated variant AR-V7 at Ser515 through XPB/CDK7. As a result, TPL suppresses the binding of AR to promoter regions in AR target genes along with reduced TFIIH and RNA Pol II recruitment. Moreover, TPL at low dose reduces the viability of prostate cancer cells expressing AR or AR-Vs. Low-dose TPL also shows a synergistic effect with enzalutamide to inhibit CRPC cell survival in vitro, and enhances the anti-cancer effect of enzalutamide on CRPC xenografts with minimal side effects. Taken together, our data demonstrate that TPL targets the transactivation activity of both full-length and truncated ARs. Our results also suggest that TPL is a potential drug for CRPC, and can be used in combination with enzalutamide to treat CRPC.
WOS关键词ANDROGEN RECEPTOR VARIANTS ; NATURAL-PRODUCT TRIPTOLIDE ; SPLICE VARIANTS ; TARGET GENES ; FULL-LENGTH ; DRUG-COMBINATION ; TERMINAL DOMAIN ; IN-VIVO ; CHEMOTHERAPY ; EXPRESSION
资助项目National Natural Science Foundation of China[31571194] ; National Natural Science Foundation of China[81672873] ; National Natural Science Foundation of China[81372168] ; National Forestry Public Welfare Industry Research Project[201204603] ; Research Innovation Team Project of Shaanxi[2013KCT-27] ; Natural Science Foundation for Universities in Jiangsu Province[BK20151396] ; National Key Research and Development Plan of China[2016YFC0902202] ; One Hundred Talent Program of Chinese Academy of Sciences[00000000] ; Research Fund of Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120164001]
WOS研究方向Research & Experimental Medicine
语种英语
WOS记录号WOS:000402093200011
出版者IVYSPRING INT PUBL
源URL[http://119.78.100.183/handle/2S10ELR8/275715]  
专题分子影像中心（筹）
通讯作者Yan, Jun; Lei, Ming
作者单位1.Chinese Acad Sci, Inst Biophys, Beijing, Peoples R China
2.Northwest A&F Univ, Coll Life Sci, Taicheng Rd, Yangling, Shaanxi, Peoples R China;
3.Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Model Anim Res Ctr, 12 Xuefu Rd, Nanjing 210061, Jiangsu, Peoples R China;
4.Nanjing Univ, MOE Key Lab Model Anim Dis Study, Model Anim Res Ctr, 12 Xuefu Rd, Nanjing 210061, Jiangsu, Peoples R China;
5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China;
推荐引用方式
GB/T 7714		 Han, Yangyang,Huang, Weiwei,Liu, Jiakuan,et al. Triptolide Inhibits the AR Signaling Pathway to Suppress the Proliferation of Enzalutamide Resistant Prostate Cancer Cells[J]. THERANOSTICS,2017,7(7):1914-1927.
APA Han, Yangyang.,Huang, Weiwei.,Liu, Jiakuan.,Liu, Dandan.,Cui, Yangyan.,...&Lei, Ming.(2017).Triptolide Inhibits the AR Signaling Pathway to Suppress the Proliferation of Enzalutamide Resistant Prostate Cancer Cells.THERANOSTICS,7(7),1914-1927.
MLA Han, Yangyang,et al."Triptolide Inhibits the AR Signaling Pathway to Suppress the Proliferation of Enzalutamide Resistant Prostate Cancer Cells".THERANOSTICS 7.7(2017):1914-1927.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

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。