Modulation of COX‐1 and COX‐2 Protein Levels by Selective and Non‐Selective NSAIDs

Abstract

Since prostaglandins are critically involved in tumorigenesis, COX inhibitors, which reduce prostaglandins, have been investigated for anti‐cancer effects. We and others have shown that the COX‐2 selective inhibitor, celecoxib, induces apoptosis in various cancer cell lines. However, the role of COX inhibition in these anti‐cancer effects remains uncertain. Previously, we reported that celecoxib and another COX‐2 selective inhibitor, etodolac, increased COX‐2 protein levels in several human cancer cell lines (A375 melanoma, CRL‐1620 glioblastoma and HT‐29 colon carcinoma). A non‐selective inhibitor, ibuprofen, failed to increase COX‐2 expression in all but A375 cells. It is well known that COX‐2 is inducible by various stimuli. However, COX‐1 is constitutive and thought to be less dynamic. Here, COX‐1 levels were examined via western blotting to determine whether they were dynamic in response to treatment with various COX inhibitors. Celecoxib treatment for 24 hours induced COX‐1 in A375 cells. In contrast, COX‐1 levels were stable in celecoxib‐treated HT‐29 cells but were decreased in CRL‐1620 cells. COX‐1 levels were unaffected by etodolac treatment in all three cells lines. Ibuprofen treatment for 24 hours induced COX‐1 in A375 and CRL‐1620 cells, but not in HT‐29 cells. Meloxicam, another COX‐2 selective inhibitor, reduced COX‐1 levels but increased COX‐2 levels in CRL‐1620 cells. These results suggest that while COX‐1 is considered a constitutive enzyme, its levels can be modulated by COX inhibitors.