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 (IC(50) FGF+group, 75±1.9μmol/l) and TGF-β1 (IC(50) TGF+group, 48±1.4μmol/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 320μmol/l celecoxib relative to the untreated control after stimulation with TGF-β1 for 3h, 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.
Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University School of Medicine, 600 Yishan Road, Shanghai 200233, China.
Fengfeng
F
Li
Shen
S
Liu
Yuanming
Y
Ouyang
Cunyi
C
Fan
Ting
T
Wang
Changqing
C
Zhang
Bingfang
B
Zeng
Yimin
Y
Chai
Xiang
X
Wang
D000818:Animals; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects*; D003094:Collagen / Q000096:biosynthesis*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010766:Phosphorylation / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D051899:Smad2 Protein; D051900:Smad3 Protein; D013449:Sulfonamides; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D003094:Collagen; D019950:Mitogen-Activated Protein Kinase 1; D000068579:Celecoxib