title: Celecoxib suppresses fibroblast growth factor-2 expression in pancreatic ductal adenocarcinoma PANC-1 cells.
abstract: The inhibition of cyclooxygenase (COX)-2 has been reported to suppress growth and induce apoptosis in human pancreatic cancer cells. Nevertheless, the precise biological mechanism of how celecoxib, a selective COX-2 inhibitor, regulates the growth and invasion of pancreatic tumors is not completely understood. It has been shown that fibroblast growth factor-2 (FGF-2) and its receptor levels correlate with the inhibition of cancer cell proliferation, migration and invasion in pancreatic ductal adenocarcinoma (PDAC). Therefore, the aim of the present study was to examine the hypothesis that the antitumor activity of celecoxib in PDAC may be exerted through modulation of FGF-2 function. In the present study, we evaluated the effects of celecoxib on the proliferation, migration, invasion and apoptosis of the PANC-1 cell line. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to examine the expression of FGF-2, FGFR-2, ERK1/2 and MMPs. In the present study, FGF-2 and FGFR-2 were expressed in PANC-1 cells and FGF-2 exerted a stimulatory effect on phosphorylated extracellular signal regulated kinase (p-ERK) expression. Celecoxib treatment suppressed FGF-2 and FGFR-2 expression and decreased MMP-2, MMP-9 and p-ERK expression in the PANC-1 cells. Furthermore, celecoxib treatment caused the resistance of PANC-1 cells to FGF-2 induced proliferation, migration and invasion ability, as well as the increase in their apoptotic rate. Our data provide evidence that targeting FGF-2 with celecoxib may be used as an effective treatment in PDAC.
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710000, P.R. China.
authors.forename: Miaosha
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Boxin
authors.initials: B
authors.lastname: Shang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000378:metabolism*; D000068579:Celecoxib / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016222:Fibroblast Growth Factor 2; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; D048052:Mitogen-Activated Protein Kinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000068579:Celecoxib