Celecoxib inhibits invasion and metastasis via a cyclooxygenase 2–independent mechanism in an in vitro model of Ewing sarcoma

Barlow, Meade; Edelman, Morris; Glick, Richard D.; Steinberg, Bettie M.; Soffer, Samuel Z.

doi:10.1016/j.jpedsurg.2012.03.031

Cited by 21 publications

(12 citation statements)

References 25 publications

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“…PTGS2, which is also known as cyclooxygenase 2, catalyzes the conversion of arachidonic acid and O 2 to prostaglandin H2, which is an important precursor in prostanoid biosynthesis. The overexpression of PTGS2 has been associated with the pathogenesis and cell mobility of various tumors, including Ewing sarcoma ( 35 ) and osteosarcoma ( 36 , 37 ). The selective PTGS2 inhibitors, celecoxib and meloxicam, have previously been demonstrated to inhibit cell proliferation and invasion in vitro and in vivo ( 35 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of critical genes and gene interaction networks that mediate osteosarcoma metastasis to the lungs

Liu

Liao

et al. 2015

Experimental and Therapeutic Medicine

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Osteosarcoma (OS) is the most commonly diagnosed bone tumor in young adults under the age of 20. Metastasis is considered an important factor underlying cancer-associated morbidity and mortality, and, as a result, the survival rate of patients with metastatic OS is low. In spite of this, the mechanisms underlying metastasis in OS are currently not well understood. The present study compared gene expression levels between five non-metastatic and four metastatic OS tumor samples, using an Affymetrix microarray. A total of 282 genes were differentially expressed in the metastatic samples, as compared with the non-metastatic samples. Of these differentially expressed genes (DEGs), 212 were upregulated and 70 were downregulated. The following DEGs were associated with metastasis: Homeobox only protein; lysosomal-associated membrane protein-3; chemokine (C-C motif) ligand-18; carcinoembryonic antigen-related cell adhesion molecule-6; keratin-19; prostaglandin-endoperoxide synthase-2; clusterin; and nucleoside diphosphate kinase-1. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses were conducted, which identified 529 biological processes (P<0.01) and 10 KEGG pathways (P<0.05) that were significantly over-represented in the metastatic samples, as compared with the non-metastatic samples. Interaction networks for the DEGs were constructed using the corresponding GO terms and KEGG pathways, and these identified numerous genes that may contribute to OS metastasis. Among the enriched biological processes, four DEGs were consistently over-represented: Jun proto-oncogene, caveolin-1, nuclear factor-κB-inhibitor-α and integrin alpha-4; thus suggesting that they may have key roles in OS metastasis, and may be considered potential therapeutic targets in the treatment of patients with OS.

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Section: Discussionmentioning

confidence: 99%

Identification of critical genes and gene interaction networks that mediate osteosarcoma metastasis to the lungs

Liu

Liao

et al. 2015

Experimental and Therapeutic Medicine

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“…Adhesion and invasion are early steps involved in the metastatic process for ovarian cancer, which has a complex molecular basis that likely involves adhesion molecules, cell surface receptors, oncogenes, chloride channels, fatty acid synthase and focal adhesion kinase [37, 38] Overexpression of COX-2 leads to phenotypic changes in cancer cells that may enhance their tumorigenic potential and invasive ability [39]. PGE2 production also favors the migration of cancer cells to endothelial cells [40].…”

Section: Discussionmentioning

confidence: 99%

The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer

et al. 2016

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Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women.

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“…COX-2 inhibitors can exert their effects by decreasing the expression of COX-2. Nevertheless, some selective COX-2 inhibitors can also provoke responses in COX-2-negative cancer cells, which could not be explained by COX-2 inhibition, however, the mechanisms of this biological effects are poorly understood (22). Celecoxib, a selective COX-2 inhibitor, has been previously shown to inhibit the growth of human pancreatic cancer cell lines (23).…”

Section: Discussionmentioning

confidence: 99%

Celecoxib suppresses fibroblast growth factor-2 expression in pancreatic ductal adenocarcinoma PANC-1 cells

Luo

Shang

et al. 2016

Oncology Reports

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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.

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Celecoxib inhibits invasion and metastasis via a cyclooxygenase 2–independent mechanism in an in vitro model of Ewing sarcoma

Cited by 21 publications

References 25 publications

Identification of critical genes and gene interaction networks that mediate osteosarcoma metastasis to the lungs

Identification of critical genes and gene interaction networks that mediate osteosarcoma metastasis to the lungs

The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer

Celecoxib suppresses fibroblast growth factor-2 expression in pancreatic ductal adenocarcinoma PANC-1 cells

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