Research Paper
Subject Category: Cancer Pharmacology
British Journal of Pharmacology (2008) 153, 1153–1161; doi:10.1038/sj.bjp.0707636; published online 17 December 2007
Celecoxib modulates adhesion of HT29 colon cancer cells to vascular endothelial cells by inhibiting ICAM-1 and VCAM-1 expression
C Dianzani1, L Brucato1, M Gallicchio1, A C Rosa1, M Collino1 and R Fantozzi1
1Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Torino, Italy
Correspondence: Dr M Collino, Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Via Pietro Giuria, 9, Torino 10125, Italy. E-mail: massimocollino@unito.it
Received 24 July 2007; Revised 10 October 2007; Accepted 5 November 2007; Published online 17 December 2007.
Abstract
Background and purpose:
Cyclooxygenase-2 (COX-2) is highly expressed during inflammation and can promote the progression of colorectal cancer. Interactions between cancer cells and vascular endothelial cells are key events in this process. Recently, the selective COX-2 inhibitor, celecoxib, was shown to inhibit expression of the adhesion molecules, ICAM-1 and VCAM-1, in the human colon cancer cell line HT29 and to inhibit adhesion of HT29 cells to FCS-coated plastic wells. Here, we evaluated the effects of celecoxib on adhesion of HT29 cells to human umbilical vein endothelial cells (HUVEC), mediated by ICAM-1 and VCAM-1, to assess further the potential protective effects of celecoxib on cancer development.
Experimental approach:
Celecoxib was incubated for 4 h with HT29 cells and HUVEC and adhesion was quantified by a computerized micro-imaging system. Expression analysis of ICAM-1 and VCAM-1 cell adhesion molecules was performed by western blot.
Key results:
Celecoxib (1 nM–10 
M) inhibited, with the same potency, adhesion of HT29 cells to resting HUVEC or to HUVEC stimulated by tumour necrosis factor-
(TNF-), mimicking inflammatory conditions. Analysis of ICAM-1 and VCAM-1 expression showed that celecoxib inhibited expression of both molecules in TNF--stimulated HUVEC, but not in resting HUVEC; inhibition was concentration-dependent and maximal (about 50%) at 10 M celecoxib.
Conclusions and implications:
In conclusion, our data show that celecoxib inhibits HT29 cell adhesion to HUVEC and expression of ICAM-1 and VCAM-1, in stimulated endothelial cells. These effects may contribute to the chemopreventive activity of celecoxib in the development of colorectal cancer.
Keywords:
celecoxib, HUVEC, HT29 cells, adhesion, ICAM-1, VCAM-1
Abbreviations:
FCS, fetal calf serum; HUVECs, human umbilical vein endothelial cells; ICAM-1, intercellular adhesion molecule-1; mAbs, monoclonal antibodies; TNF-, tumour necrosis factor-; VCAM-1, vascular cell adhesion molecule-1
