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学科主题: 临床医学
题名:
A Novel Sulindac Derivative Lacking Cyclooxygenase-Inhibitory Activities Suppresses Carcinogenesis in the Transgenic Adenocarcinoma of Mouse Prostate Model
作者: Zhang, Yong3; Zhang, Jinhui; Wang, Lei; Quealy, Emily; Gary, Bernard D.2; Reynolds, Robert C.2; Piazza, Gary A.2; Lue, Junxuan1
刊名: CANCER PREVENTION RESEARCH
发表日期: 2010-07-01
DOI: 10.1158/1940-6207.CAPR-09-0273
卷: 3, 期:7, 页:885-895
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; FAMILIAL ADENOMATOUS POLYPOSIS ; CANCER CELLS ; ANDROGEN RECEPTOR ; COLON-CANCER ; COLORECTAL ADENOMAS ; LUNG-CANCER ; PREVENTION ; NSAIDS ; TRIAL
英文摘要:

Nonsteroidal anti-inflammatory drugs including sulindac are well documented to be highly effective for cancer chemoprevention. However, their cyclooxygenase (COX)-inhibitory activities cause severe gastrointestinal, renal, and cardiovascular toxicities, limiting their chronic use. Recent studies suggest that COX-independent mechanisms may be responsible for the chemopreventive benefits of nonsteroidal anti-inflammatory drugs and support the potential for the development of a novel generation of sulindac derivatives lacking COX inhibition for cancer chemoprevention. A prototypic sulindac derivative with a N,N-dimethylammonium substitution called sulindac sulfide amide (SSA) was recently identified to be devoid of COX-inhibitory activity yet displays much more potent tumor cell growth-inhibitory activity in vitro compared with sulindac sulfide. In this study, we investigated the androgen receptor (AR) signaling pathway as a potential target for its COX-independent antineoplastic mechanism and evaluated its chemopreventive efficacy against prostate carcinogenesis using the transgenic adenocarcinoma of mouse prostate model. The results showed that SSA significantly suppressed the growth of human and mouse prostate cancer cells expressing AR in strong association with G(1) arrest, and decreased AR level and AR-dependent transactivation. Dietary SSA consumption dramatically attenuated prostatic growth and suppressed AR-dependent glandular epithelial lesion progression through repressing cell proliferation in the transgenic adenocarcinoma of mouse prostate mice, whereas it did not significantly affect neuroendocrine carcinoma growth. Overall, the results suggest that SSA may be a chemopreventive candidate against prostate glandular epithelial carcinogenesis. Cancer Prev Res; 3(7); 885-95. (C) 2010 AACR.

语种: 英语
所属项目编号: R01CA126880 ; R01CA131378
项目资助者: Hormel Foundation, National Cancer Institute
WOS记录号: WOS:000279556900011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65189
Appears in Collections:北京大学第一临床医学院_泌尿外科_期刊论文

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作者单位: 1.Univ Minnesota, Hormel Inst, Austin, MN 55912 USA
2.Peking Univ, Peking Univ Hosp 1, Inst Urol, Beijing 100871, Peoples R China
3.So Res Inst, Birmingham, AL 35255 USA

Recommended Citation:
Zhang, Yong,Zhang, Jinhui,Wang, Lei,et al. A Novel Sulindac Derivative Lacking Cyclooxygenase-Inhibitory Activities Suppresses Carcinogenesis in the Transgenic Adenocarcinoma of Mouse Prostate Model[J]. CANCER PREVENTION RESEARCH,2010,3(7):885-895.
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