Celecoxib decreases expression of the adhesion molecules ICAM-1 and VCAM-1 in a colon cancer cell line (HT29).
Br J Pharmacol
; 153(5): 870-8, 2008 Mar.
Article
em En
| MEDLINE
| ID: mdl-18084318
ABSTRACT
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. EXPERIMENTALAPPROACH:
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. KEYRESULTS:
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 NH(2) 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.
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Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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Sulfonamidas
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Inibidores de Ciclo-Oxigenase
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Molécula 1 de Adesão Intercelular
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Molécula 1 de Adesão de Célula Vascular
Limite:
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article