Effect of celecoxib on proliferation, collagen expression, ERK1/2 and SMAD2/3 phosphorylation in NIH/3T3 fibroblasts

In the present study, the effects of celecoxib on proliferation, collagen expression, ERK1/2 and SMAD2/3 phosphorylation in NIH/3T3 fibroblasts were investigated. NIH/3T3 fibroblasts stimulated with fibroblast growth factor-2 (FGF-2) or transforming growth factor-β1 (TGF-β1) were examined in the presence of celecoxib. Proliferation was assessed by MTT assays; ERK1/2 expression and SMAD2/3 expression were assessed by quantitative RT-PCR and western blotting; ERK1/2 phosphorylation and SMAD2/3 phosphorylation were assessed by western blot analysis. The results indicated that celecoxib could suppress cell proliferation stimulated by FGF-2 (IC50 FGF + group, 75 ± 1.9 μmol/l) and TGF-β1 (IC50 TGF + group, 48 ± 1.4 μmol/l), by inhibiting ERK1/2 phosphorylation but not ERK1/2 expression. Celecoxib also suppressed collagen expression (0.35-fold COL3 and 0.43-fold COL1 at 320 μmol/l celecoxib relative to the untreated control after stimulation with TGF-β1 for 3 h, P < 0.01), by inhibiting SMAD2/3 phosphorylation but not SMAD2/3 expression. The suppression of NIH/3T3 fibroblast proliferation and collagen expression upon stimulation by FGF-2 and TGF-β1 is likely a result of the inhibition of ERK1/2 and SMAD2/3 phosphorylation by celecoxib.