Celecoxib decreases expression of the adhesion molecules ICAM‐1 and VCAM‐1 in a colon cancer cell line (HT29)

Background and purpose:

We investigated the ability of celecoxib, a selective cyclooxygenase‐2 (COX‐2) inhibitor, to modulate expression of ICAM‐1 and VCAM‐1 in the colon cancer cell line HT29.

Experimental approach:

We analysed the effect of celecoxib on ICAM‐1 and VCAM‐1 protein and mRNA expression in HT29 cells. Experiments were performed in the presence of mitogen‐activated protein kinases (MAPK) inhibitors to evaluate the involvement of these kinases in this phenomenon. We evaluated adhesion of HT29 cells to FCS‐coated plastic wells in the presence of celecoxib or MAPK inhibitors. Furthermore, we studied the effect of celecoxib on apoptosis.

Key results:

Celecoxib down‐regulated ICAM‐1 and VCAM‐1 expression in HT29 cells in a time‐ and dose‐dependent way. Celecoxib reduced activation of p38 and p55 c‐Jun terminal NH₂ kinase (JNK) MAPKs, but did not affect p46 JNK or p42/44 MAPK phosphorylation. Pretreatment with SB202190 or SP600125, specific inhibitors of p38 and JNK MAPKs, respectively, reduced ICAM‐1 and VCAM‐1 expression in HT29 cells dose‐dependently. Adhesion of HT29 cells to FCS‐coated plastic wells was inhibited dose‐dependently by celecoxib, and also by SB202190 and SP600125. Celecoxib showed a pro‐apoptotic effect, inducing Bax and BID but down‐regulating Bcl‐2.

Conclusions and implications:

Our findings show that celecoxib caused down‐regulation of ICAM‐1 and VCAM‐1, affecting the adhesive properties of HT29 cells in a COX‐2 independent way, inhibiting p38 and p55 MAPKs and activating a pro‐apoptotic pathway.

DOI: 10.1038/sj.bjp.0707634

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