scholarly journals The Association between Functional Polymorphisms of COX-2 and Serum PGE2 Level in ESCC Patients in North of Iran

2019 ◽  
Vol 9 (1) ◽  
pp. 133
Author(s):  
Maryam Sadegh Sheshpoli ◽  
Safoura Khajeniazie ◽  
Masoud Khoshnia ◽  
Nasser Behnampour ◽  
Mohsen Saeedi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Protein Expression ◽  
Roc Curve Analysis ◽  
Downstream Signaling ◽  
Functional Polymorphisms ◽  
Pge2 Level ◽  
North Of Iran ◽  
Mrna And Protein Expression ◽  
Golestan Province ◽  
Cox 2

Background: Esophageal cancer is recognized as one of the most fatal diseases around the world. Many factors are involved in the development of esophageal cancer, including genetic factors and inflammation. Cyclooxygenase-2 (COX-2) and its downstream signaling are the most important proinflammatory factors contributing to cancer. The present study aimed to evaluate the relationship between the polymorphisms and expression of COX-2 and prostaglandin-E2 (PGE2) level in patients with esophageal squamous cell carcinoma (ESCC) in Golestan Province (Iran), situated on the “esophageal cancer belt”. Methods: In this case-control study, blood and biopsy samples were obtained from ESCC patients and healthy controls. The COX-2 polymorphisms for -1195, -1290, -765, and +8473 SNPs were assayed using PCR-RFLP assay, while the level of PGE2 was measured using an ELISA kit. In addition, real-time PCR assay and immunohistochemistry (IHC) were performed to assay mRNA and protein expression of COX-2, respectively. Results: An association was found between 8473TC genotype and risk of ESCC (OR= 5.417, P= 0.036). In addition, mRNA and protein expression of COX-2 in ESCC patients was higher than the controls (P=0.001 and P=0.048, respectively). Based on the findings, the level of PGE-2 was significantly higher in ESCC patients, compared to the controls (P= 0.045). However, ROC curve analysis revealed PGE2 is a weak biomarker for diagnosis of ESCC. There was a significant relationship between the level of PGE2 and 8473CC, 8473TC, -765CC, and -1290AA genotypes (P= 0.028, P= 0.022, P= 0.024, and P= 0.011, respectively). Conclusion: Based on our results, functional polymorphisms of COX-2 (8473CC, 8473TC, - 765CC, and -1290AA) increase PGE2 level and carriers of these polymorphisms might be more susceptible to ESCC.

scholarly journals Apurinic/apyrimidinic endonuclease-1 is associated with angiogenesis and VEGF production via upregulation of COX-2 expression in esophageal cancer tissues

2014 ◽  
Vol 306 (3) ◽  
pp. G183-G190 ◽  
Author(s):  
Hiroyuki Nagoya ◽  
Seiji Futagami ◽  
Mayumi Shimpuku ◽  
Atsushi Tatsuguchi ◽  
Taiga Wakabayashi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Protein Expression ◽  
Cell Lines ◽  
Excision Repair ◽  
Multifunctional Protein ◽  
Expression Levels ◽  
Key Enzyme ◽  
Mrna And Protein Expression ◽  
Cox 2 ◽  
Cancer Tissues

Apurinic/apyrimidinic endonuclease-1 (APE-1) is a key enzyme responsible for DNA base excision repair and is also a multifunctional protein such as redox effector for several transcriptional factors. Our study was designed to investigate APE-1 expression and to study its interaction with cyclooxygenase (COX)-2 expression and VEGF production in the esophageal cancer. The expression of APE-1, COX-2, monocyte chemoattractant protein (MCP)-1, CC-chemokine receptor (CCR)2, and VEGF were evaluated by immunohistochemistry in 65 human esophageal squamous cell carcinoma (ESCC) tissues. Real-time PCR and Western blotting were performed to detect mRNA and protein expression of APE-1 and p-signal transducer and activator of transcription 3 (STAT3) expression in MCP-1-stimulated ESCC cell lines (KYSE 220 and EC-GI-10). siRNA for APE-1 was treated to determine the role of APE-1 in the regulation of COX-2 expression, VEGF production, and antiapoptotic effect against cisplatin. In human ESCC tissues, nuclear localization of APE-1 was observed in 92.3% (60/65) of all tissues. There was a significant relationship ( P = 0.029, R = 0.49) between nuclear APE-1 and cytoplasmic COX-2 expression levels in the esophageal cancer tissues. In KYSE 220 and EC-GI-10 cells, MCP-1 stimulation significantly increased mRNA and protein expression of APE-1. Treatment with siRNA for APE-1 significantly inhibited p-STAT3 expression levels in MCP-1-stimulated cells. Furthermore, treatment of siRNA for APE-1 significantly reduced COX-2 expression and VEGF production in MCP-1-stimulated esophageal cancer cell lines. Treatment with APE-1 siRNA significantly increased apoptotic levels in cisplatin-incubated KYSE 220 and EC-GI-10 cells. We concluded that APE-1 is overexpressed and associated with COX-2 expression and VEGF production in esophageal cancer tissues.

Akt regulates COX-2 mRNA and protein expression in mutated-PTEN human endometrial cancer cells

2004 ◽  
Author(s):  
Marie-Eve St-Germain ◽  
Veronique Gagnon ◽  
Isabelle Mathieu ◽  
Sophie Parent ◽  
Eric Asselin
Keyword(s):  
Endometrial Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Mrna And Protein Expression ◽  
Cox 2

Esophageal cancer mortality in a high-incidence area (Golestan Province, north of Iran)

2018 ◽  
Vol 27 (6) ◽  
pp. 577-578 ◽  
Author(s):  
Hamed E. Leylabadlo ◽  
Nasim A. Faezi ◽  
Abed Z. Bialvaei ◽  
Hossein S. Kafil
Keyword(s):  
Esophageal Cancer ◽  
Cancer Mortality ◽  
High Incidence ◽  
North Of Iran ◽  
Golestan Province ◽  
High Incidence Area

scholarly journals Glucose Promotes the Production of Interleukine-1β and Cyclooxygenase-2 in Mesangial Cells via Enhanced (Pro)Renin Receptor Expression

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5557-5565 ◽  
Author(s):  
Jiqian Huang ◽  
Helmy M. Siragy
Keyword(s):  
Angiotensin Ii ◽  
Protein Expression ◽  
Receptor Antagonist ◽  
High Glucose ◽  
Small Interfering Rna ◽  
Mesangial Cells ◽  
Receptor Blockade ◽  
Mrna And Protein Expression ◽  
Cox 2 ◽  
Interfering Rna

Abstract (Pro)renin receptor (PRR) is present in renal glomeruli, and its expression is up-regulated in diabetes. Similarly, renal inflammation is increased in the presence of hyperglycemia. The linkage between PRR and renal inflammation is not well established. We hypothesized that glucose-induced up-regulation of PRR leads to increased production of the proinflammatory factors IL-1β and cyclooxygenase-2 (COX-2). Studies were conducted in rat mesangial cells (RMCs) exposed to 30 mmd-glucose for 2 wk followed by PRR small interfering RNA knockdown, IL-1 receptor blockade with IL-1 receptor antagonist or angiotensin II type 1 receptor blockade with valsartan. The results showed that d-glucose treatment up-regulates prorenin, renin, angiotensin II, PRR, IL-1β, and COX-2 mRNA and protein expression and increases phosphorylation of ERK1/2, c-Jun N-terminal kinase, c-Jun, and nuclear factor-κB (NF-κB) p65 (serine 276,468 and 536), respectively. PRR small interfering RNA attenuated PRR, IL-1β, and COX-2 mRNA and protein expressions and significantly decreased angiotensin II production and phosphorylation of ERK1/2 and NF-κB p65 associated with high glucose exposure. Similarly, IL-1 receptor antagonist significantly reduced COX-2 mRNA and protein expression induced by high glucose. COX-2 inhibition reduced high-glucose-induced PRR expression. We conclude that glucose induces the up-regulation of PRR and its ligands prorenin and renin, leading to increased IL-1β and COX-2 production via the angiotensin II-dependent pathway. It is also possible that PRR could enhance the production of these inflammatory cytokines through direct stimulation of ERK1/2-NF-κB signaling cascade.

scholarly journals Rapid and transient induction of cyclo-oxygenase 2 by epidermal growth factor in human amnion-derived WISH cells

1997 ◽  
Vol 321 (3) ◽  
pp. 677-681 ◽  
Author(s):  
Douglas J. PERKINS ◽  
Douglas A. KNISS
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Protein Expression ◽  
De Novo ◽  
Tnf Α ◽  
Mrna And Protein Expression ◽  
Epidermal Growth ◽  
Cox 2 ◽  
Dose Dependent ◽  
Cox 1

The central enzyme in the prostaglandin (PG) biosynthetic cascade is PGH2 synthase or cyclo-oxygenase (COX). At present, two distinct isoforms of PGH2 synthase/COX have been identified: COX-1 and COX-2. In many systems, COX-1 is a constitutively expressed isoform that is responsible for normal physiological production of PGs, whereas COX-2 is an inducible isoform that responds to cytokines, endotoxin and growth factors by producing high levels of PGs. The regulation of COX-2 mRNA and protein, and the subsequent production of PGE2, were therefore examined in amnion-derived WISH cells stimulated with epidermal growth factor (EGF). Treatment of WISH cells with EGF (0.01Ő100 ng/ml) elicited dose-dependent synthesis of COX-2 mRNA and protein de novo. In addition, stimulation of WISH cells with EGF (10 ng/ml) induced steady-state levels of COX-2 mRNA and protein that appeared within 30 min and then declined rapidly to near baseline levels within 2Ő4 h. In contrast, COX-1 protein was unchanged in response to treatment with EGF. PGE2 production was also rapid and transient. Preincubation of cells with the novel COX-2 enzymic inhibitor NS-398 (10-5Ő10-10 M) completely prevented PGE2 formation in a dose-dependent manner. Preincubation of cells in dexamethasone (Dex; 0.1 ƁM), however, resulted in only a 31% decrease in PGE2 formation in response to EGF (10 ng/ml) while completely attenuating PGE2 biosynthesis in tumour necrosis factor α (TNF-α)-stimulated cells. In addition, Dex (0.1 ƁM) was only partly effective at preventing EGF-induced COX-2 mRNA and protein expression de novo, whereas Dex completely inhibited TNF-α-promoted COX-2 mRNA and protein expression. Thus the results presented here demonstrate that EGF induces the rapid but transient expression of COX-2 mRNA and protein and the subsequent production of PGE2 in WISH cells.

Over-Expression of RPS3 Promotes Acute Lymphoblastic Leukemia Growth and Progress By Down-Regulating COX-2 through NF-κb Pathway

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3927-3927
Author(s):  
Wang Hua ◽  
Lu Yue ◽  
Shi Dingbo
Keyword(s):  
Cell Cycle ◽  
Acute Lymphoblastic Leukemia ◽  
Protein Expression ◽  
Cell Lines ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Leukemia Cell Lines ◽  
Mrna And Protein Expression ◽  
Cox 2

Abstract The Ribosome protein S3 (RPS3) is a component of 40S ribosomal subunit, which is important in ribosomal maturation.In addition, RPS3 plays a central role in the regulation of cell cycle,proliferation,migration,DNA repair,and apoptosis.Recent study has also been reported that RPS3 is secreted as a homodimer in cancer cells. The increased level of secreted RPS3 was detected in more malignant cells.These findings suggest that the RPS3 protein is an indicator of malignant tumors.Therefore, we studied the roles and the functions mechanisms of RPS3 in leukemia in order to understand whether RPS3could be a key target for leukemia therapy. qRT-PCR and western blot analysis were carried out in a small cohort of acute lymphoblastic leukemia patients(ALL) and multiple leukemia cell lines to evaluate RPS3 mRNA and protein expression levels.To assess its biological functions relevance, its expression was down modulated by transient RNA interference in ALL cell lines.Our results show that RPS3 mRNA and protein expression is higher in both ALL patients and the ALL cell lines when compared to the healthy donors peripheral blood mononuclear cell or myeloid leukemia cell lines. Correspondence with this, the ALL patients with higher expression of RPS3 had shorter overall survival than those with lower expression of RPS3 (25.1% vs. 63.4%, P<0.001, for 5 year-OS).Furthermore,blocking RPS3 activity in four ALL cell lines, by either knockdown or treatment with the RPS3 inhibitor, causes significant decrease in their cell proliferation.This decrease in cell proliferation was coupled with both an induction of the G1/S cell cycle arrest and with an increase of apoptosis induced in the leukemia population. In vivo,we also found that knockdown of RPS3 significantly inhibited tumor growth in a ALL xenograft mouse model. Finally, mechanism studies showed that RPS3 knockdown in ALL cells triggered suppression of COX-2 expression and its down-stream targets PGE2 release,inhibited COX-2 promoter activity by decreased P50 /P65 Binding to cox2 promotor. In conclusion,our results suggest that overexpression of RPS3 promotes acute lymphoblastic leukemia growth and progress by up-regulating COX-2 through NF-κB pathway. and that targeting RPS3could be an attractive strategy for ALL therapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Differential Regulation of Prostaglandin Production Mediated by Corticotropin-Releasing Hormone Receptor Type 1 and Type 2 in Cultured Human Placental Trophoblasts

Endocrinology ◽  
2008 ◽  
Vol 149 (6) ◽  
pp. 2866-2876 ◽  
Author(s):  
Lu Gao ◽  
Chunmei Lu ◽  
Chen Xu ◽  
Yi Tao ◽  
Binhai Cong ◽  
...  
Keyword(s):  
Protein Expression ◽  
Synthetic Enzymes ◽  
Cytosolic Phospholipase ◽  
Pge2 Release ◽  
Key Enzyme ◽  
Mrna And Protein Expression ◽  
Cox 2

Prostaglandin (PG) production by intrauterine tissues plays a key part in the control of pregnancy and parturition. The present study was to investigate the role of placenta-derived CRH and CRH-related peptides in the regulation of PG synthesis and metabolism. We found that placental trophoblasts expressed both CRH-R1 and CRH-R2. Treatment of cultured placental cells with either a CRH or urocortin I (UCNI) antibody resulted in a significant decrease in PGE2 release. Both CRH and UCNI antibodies significantly decreased mRNA and protein expression of synthetic enzymes cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX)-2 and increased mRNA and protein expression of 15-hydroxyprostaglandin dehydrogenase (PGDH), the key enzyme of PG metabolism. CRH-R1/-R2 antagonist astressin and CRH-R1 antagonist antalarmin significantly inhibited PGE2 release, whereas CRH-R2 antagonist astressin-2b had no effect on PGE2 release. Administration of astressin decreased expression of cPLA2 but had no effect on COX-2 expression. Antalarmin reduced cPLA2 and COX-2 expression, whereas astressin-2b did not alter cPLA2 expression but increased COX-2 expression. PGDH expression was enhanced by these three antagonists. Cells treated with exogenous CRH and UCNI showed an increase in PGE2 release and expression of cPLA2 and COX-2 but a decrease in PGDH expression. UCNII and UCNIII had no effect on PGE2 release but decreased COX-2 and PGDH expression. Our results suggested CRH and CRH-related peptides act on CRH-R1 and CRH-R2 to exert different effects on PG biosynthetic enzymes cPLA2 and COX-2 and thereby modulate output of PGs from placenta, which would be important for controlling pregnancy and parturition.

scholarly journals Qigesan reduces the motility of esophageal cancer cells via inhibiting Gas6/Axl and NF-κB expression

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Lingyu Kong ◽  
Zhongbing Wu ◽  
Yang Zhao ◽  
Xin Lu ◽  
Huijuan Shi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Matrix Metalloproteinase ◽  
Protein Expression ◽  
Cell Lines ◽  
Cultured Cells ◽  
Matrix Metalloproteinase 2 ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Protein Activation ◽  
Downstream Signaling

AbstractThe present study is mainly to explore the mechanism that how Qigesan (QGS) affects the movement capacity of esophageal cancer (EC) cell. QGS incubates ECA109 and TE1 cell lines and detecting the motility of tumor cells by different experiments. Growth arrest-specific 6 (Gas6) and Anexelekto (Axl) were co-localized, and then detecting Gas6, Axl signaling pathway, and protein expression after QGS intervention. Similarly, Observing the signal localization and protein expression of P-phosphoinositide3-kinases (PI3K), P-AKT protein kinase B (AKT), P-nuclear factor-kappa B (NF-κB), matrix metalloproteinase-2 (MMP2), and matrix metalloproteinase-9 (MMP9). The results showed that the concentration of QGS was less than 200 ug/ml, and the cultured cells did not exceed 24 h, that no obvious cytotoxicity was observed. QGS significantly inhibited the mobility of ECA109 and TE1 cell lines in the concentration-dependent manner. In addition, QGS can regulate the Gas6/Axl pathway, inhibit the formation and localization of the Gas6/Axl complex, and reduce the protein activation of PI3K/AKT, NF-κB, MMP2, and MMP9. Experimental innovation shows that QGS can significantly slow down the mobility of EC cells by regulating the Gas6/Axl complex and downstream signaling pathways, and provides a theoretical basis for the pharmacological effects of QGS in the therapy of EC.

scholarly journals Soy Saponins Meditate the Progression of Colon Cancer in Rats by Inhibiting the Activity of β-Glucuronidase and the Number of Aberrant Crypt Foci but Not Cyclooxygenase-2 Activity

ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Yu-Wei Guo ◽  
Yue-Hwa Chen ◽  
Wan-Chun Chiu ◽  
Hsiang Liao ◽  
Shyh-Hsiang Lin
Keyword(s):  
Colon Cancer ◽  
Protein Expression ◽  
Research Methods ◽  
Colonic Mucosa ◽  
Cyclooxygenase 2 ◽  
Aberrant Crypt Foci ◽  
Preneoplastic Lesions ◽  
Pge2 Level ◽  
Cox 2 ◽  
Different Doses

Objective. The effect of extracted crude soybean saponins on preneoplastic lesions, aberrant crypt foci (ACF), and the related mechanism were investigated. Research Methods and Procedures. Rats were assigned into five groups according to different doses of extracted crude soybean saponins and received 1,2-dimethylhydrazine (DMH) injection in week 5. In week 15, all rats were sacrificed. The number of ACFs, the cyclooxygenase-2 (COX-2) protein expression, the level of prostaglandins E2 (PGE2), and the activity of β-glucuronidase were examined. Results. Results revealed that the consumption of extracted crude soybean saponins decreased the number of ACFs and the activity of β-glucuronidase in rats, while the expression of COX-2 protein and PGE2 level were not affected. Conclusions. Soybean saponins were effective in inhibiting colon cancer by downregulating the activity of β-glucuronidase in colonic mucosa but not the COX-2 protein expression and PGE2 level.

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