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.

Molecular Ultrasound Imaging Depicts the Modulation of Tumor Angiogenesis by Acetylsalicylic Acid

“…Other studies showed a correlation between COX-2 expression and tumor VEGF concentration [ 40 , 41 ], suggesting a COX-2-dependent reduction in VEGFR-2 expression. Another mechanism leading to a reduced VEGFR-2 expression could be the inhibition of FGF via COX-2 [ 42 , 43 ], as decreased FGF expression was shown to decrease VEGFR-2 expression [ 44 ].…”

Role of Basic Fibroblast Growth Factor in Cancer: Biological Activity, Targeted Therapies, and Prognostic Value

“…Pro-angiogenic factors such as VEGF and bFGF largely contribute to the proliferation, invasion, and migration of pancreatic cancer cells [ 118 ]. In contrast, Quercetin-3-O-glucoside and Celecoxib acted as bFGF inhibitors, avoiding the expansion of local metastasis induced by various growth factors in pancreatic cancers and promoting their use as an effective adjuvant to boost chemotherapeutic agents [ 119 , 120 ]. Moreover, Chen et al, elucidated the interplay between the heparanase (HPA)/syndecan-1 (SDC1) axis and bFGF, suggesting HPA/SDC1 silencing as a valuable therapeutic strategy in decreasing bFGF [ 121 ].…”