Diclofenac attenuates Wnt/β-catenin signaling in colon cancer cells by activation of NF-κB

被引：59

作者：

Cho, M

Gwak, J

Park, S

Won, J

Kim, DE

Yea, SS

Cha, IJ

Kim, TK

Shin, JG

Oh, S ^{[1
]}

机构：

[1] Inje Univ, Coll Med, Dept Pharmacol, Pusan 633165, South Korea

[2] Inje Univ, PharmcoGenom Res Ctr, Pusan 633165, South Korea

[3] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea

[4] Dong Eui Univ, Dept Biotechnol & Bioengn, Pusan 614714, South Korea

来源：

FEBS LETTERS | 2005年 / 579卷 / 20期

关键词：

Wnt/beta-catenin signaling; nuclear factor-kappa B; diclofenac; colon cancer cell;

D O I：

10.1016/j.febslet.2005.06.049

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The dysregulation of Wnt/beta-catenin signaling and subsequent upregulation of beta-catenin response transcription (CRT) occur frequently in colon cancer cells. Non-steroidal anti-inflammatory drugs (NSAIDs) can repress CRT in colorectal cancer, but little is known about the mechanism of action. We show that the NSAID diclofenac inhibits Wnt/beta-catenin signaling without altering the level of beta-catenin protein and reduces the expression of beta-catenin/TCF-dependent genes. Diclofenac induced the degradation of I kappa B alpha, which increased free nuclear factor kappa B (NF-kappa B) in cells. Also, the ectopic expression of p65, which is a component of NF-kappa B, suppressed CRT. Our findings suggest that diclofenac inhibits Wnt/beta-catenin signaling via the activation of NF-kappa B in colon cancer cells. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：4213 / 4218

页数：6

共 32 条

[1] beta-catenin is a target for the ubiquitin-proteasome pathway [J].