Celecoxib suppresses fibroblast proliferation and collagen expression             by inhibiting ERK1/2 and SMAD2/3 phosphorylation.
This study aimed to investigate whether celecoxib suppresses fibroblast proliferation and collagen expression by inhibiting extracellular signal-regulated kinase 1/2 (ERK1/2) and SMAD2/3 phosphorylation. Celecoxib was added to NIH/3T3 fibroblasts stimulated by fibroblast growth factor-2 (FGF-2) or transforming growth factor-β1 (TGF‑β1). NIH/3T3 fibroblast proliferation and viability were assessed by MTT assays; ERK1/2 expression and SMAD2/3 expression were assessed by quantitative RT-PCR and Western blot analysis. The results indicated that celecoxib suppressed cell proliferation (IC50 FGF+ group, 75 ± 1.9 µmol/l) stimulated by FGF-2, and also inhibited cell viability (IC50 FGF- group, 252 ± 2.3 µmol/l) by inhibiting ERK1/2 phosphorylation but not ERK1/2 expression. In addition, celecoxib treatment led to the apoptosis of NIH/3T3 fibroblasts (IC50 FGF- group, 35 ± 1.4 µmol/l). Celecoxib also suppressed collagen expression (0.35-fold COL3 and 0.43-fold COL1 with 320 µmol/l celecoxib relative to the untreated group following stimulation for 3 h, p<0.01) when stimulated by TGF‑β1, by inhibiting SMAD2/3 phosphorylation but not SMAD2/3 expression. Celecoxib is capable of inhibiting ERK1/2 and SMAD2/3 phosphorylation, which is responsible for NIH/3T3 fibroblast proliferation and collagen expression.
Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University, Shanghai 200233, PR China.
Fengfeng
F
Li
Cunyi
C
Fan
Bingfang
B
Zeng
Changqing
C
Zhang
Yimin
Y
Chai
Shen
S
Liu
Yuanming
Y
Ouyang
D000818:Animals; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010766:Phosphorylation / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D051899:Smad2 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051900:Smad3 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / 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; D048052:Mitogen-Activated Protein Kinase 3; D000068579:Celecoxib