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

Abstract

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 IkappaBalpha, which increased free nuclear factor kappaB (NF-kappaB) in cells. Also, the ectopic expression of p65, which is a component of NF-kappaB, suppressed CRT. Our findings suggest that diclofenac inhibits Wnt/beta-catenin signaling via the activation of NF-kappaB in colon cancer cells.