We examined the effect of celecoxib on the expression of T-cell factors (TCFs) to clarify the mechanism by which celecoxib Suppress beta-catenin/TCF-dependent transcriptional activity without reducing the level of beta-catenin protein, using HCT-116 cells. Celecoxib Suppressed the expression of TCF-1 and TCF-4 in a time-dependent manner. Pretreatment of cells with the proteasome inhibitor MG132 inhibited the loss of TCF-1 and TCF-4 induced by celecoxib. Suggesting that celecoxib induced the proteasome-dependent degradation of TCF-1 and TCF-4. beta-Catenin/TCF-dependent transcriptional activity was significantly decreased after the treatment with celecoxib for 6 h and the pretreatment of the cells with MG132 attenuated the effect of celecoxib. Further, celecoxib also suppressed the expression of TCF-1 and TCF-4 in another colon cancer cell line, DLD-1. Our results suggest that TCF-1 and TCF-4 degradation may involve the inhibition of the Wnt/beta-catenin signaling pathway induced by celecoxib. (C) 2008 Elsevier Inc. All rights reserved.