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

The dysregulation of Wnt/β-catenin signaling and subsequent upregulation of β-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/β-catenin signaling without altering the level of β-catenin protein and reduces the expression of β-catenin/TCF-dependent genes. Diclofenac induced the degradation of IκBα, which increased free nuclear factor κB (NF-κB) in cells. Also, the ectopic expression of p65, which is a component of NF-κB, suppressed CRT. Our findings suggest that diclofenac inhibits Wnt/β-catenin signaling via the activation of NF-κB in colon cancer cells.