• Proceedings of the PSK Conference
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• 2003.04a
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• pp.198-199
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• 2003

Chronic inflammatory processes are associated with pathology of Alzheimer's disease(AD). The expression of both cyclooxygenase-2(COX-2) and phospholipase A2(PLA2) appears to be strongly activated during AD, indicating the importance of inflammatory gene pathways as a response to brain injury. Stimulation of heterotrimeric G protein-coupled receptors including muscarinic receptors activates cytosolic PLA2 and receptor-mediated activation of PLA2 generates free fatty acids (i.e., arachidonic acid). (omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8301-8310
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• 2014

Background: Published data regarding associations between the -765G>C polymorphism in cyclooxygenase-2 (COX-2) gene and digestive system cancer risk have been inconclusive. The aim of this study was to comprehensively evaluate the genetic risk of the -765G>C polymorphism in the COX-2 gene for digestive system cancer. Materials and Methods: A search was performed in Pubmed, Medline (Ovid), Embase, CNKI, Weipu, Wanfang and CBM databases, covering all studies until Feb 10, 2014. Statistical analysis was performed using Revman5.2. Results: A total of 10,814 cases and 16,174 controls in 38 case-control studies were included in this meta-analysis. The results indicated that C allele carriers (GC+CC) had a 20% increased risk of digestive system cancer when compared with the homozygote GG (odds ratio (OR)=1.20, 95% confidence interval (CI), 1.00-1.44 for GC+CC vs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers (GC+CC) in Asians (OR = 1.46, 95% CI=1.07-2.01, and p=0.02) and Africans (OR=2.12, 95% CI=1.57-2.87, and p< 0.00001), but not among Caucasians, Americans and mixed groups. For subgroup analysis by cancer type (GC+CC vs GG), significant associations were found between the -765G>C polymorphism and higher risk for gastric cancer (OR=1.64, 95% CI=1.03-2.61, and p=0.04), but not for colorectal cancer, oral cancer, esophageal cancer, and others. Regarding study design (GC+CC vs GG), no significant associations were found in then population-based case-control (PCC), hospital-based case-control (HCC) and family-based case-control (FCC) studies. Conclusions: This meta-analysis suggested that the -765G>C polymorphism of the COX-2 gene is a potential risk factor for digestive system cancer in Asians and Africans and gastric cancer overall.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.3
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• pp.139-144
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• 2010

In this study, we evaluated the role of apurinic/apyrimidinic endonuclease1/redox factor-1 (Ref-1) on the tumor necrosis factor-$\alpha$ (TNF-$\alpha$) induced cyclooxygenase-2 (COX-2) expression using A549 lung adenocarcinoma cells. TNF-$\alpha$ induced the expression of COX-2 in A549 cells, but did not induce BEAS-2B expression. The expression of COX-2 in A549 cells was TNF-$\alpha$ dose-dependent (5~100 ng/ml). TNF-$\alpha$-stimulated A549 cells evidenced increased Ref-1 expression in a dose-dependent manner. The adenoviral transfection of cells with AdRef-1 inhibited TNF-$\alpha$-induced COX-2 expression relative to that seen in the control cells ($Ad{\beta}gal$). Pretreatment with $10\;{\mu}M$ of SB203580 suppressed TNF-$\alpha$-induced COX-2 expression, thereby suggesting that p38 MAPK might be involved in COX-2 expression in A549 cells. The phosphorylation of p38 MAPK was increased significantly after 5 minutes of treatment with TNF-$\alpha$, reaching a maximum level at 10 min which persisted for up to 60 min. However, p38MAPK phosphorylation was markedly suppressed in the Ref-1-overexpressed A549 cells. Taken together, our results appear to indicate that Ref-1 negatively regulates COX-2 expression in response to cytokine stimulation via the inhibition of p38 MAPK phosphorylation. In the lung cancer cell lines, Ref-1 may be involved as an important negative regulator of inflammatory gene expression.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.46-52
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• 2023

The most abundant flavanone of grapefruits, naringenin (NN), is well known for its hepatoprotective, anti-lipid peroxidation and anti-carcinogenic effects. We generated three derivatives from NN using this technique in previous studies. Among them, it was confirmed that naringenin-7-O-phosphate (N7P), whose biological and physicochemical properties were not reported, showed a water solubility 45 times higher than that of NN. Therefore, in this study, the anti-inflammatory activity was evaluated in RAW 264.7 cells to investigate the potential physiological activity of N7P. As a result, N7P showed nitric oxide (NO) inhibitory activity at concentrations that did not show toxicity. In addition, prostaglandin E₂ (PGE₂) showed significant inhibitory activity from the lowest concentration of 12.5 μM and showed increased inhibitory activity compared to NN. In addition, as a result of western blot, N7P showed increased cyclooxygenase-2 (COX-2) inhibitory activity than NN, and effectively inhibited NO and PGE₂ by significantly inhibiting their expression pathways. N7P also inhibited inflammatory cytokines, including tumor necrosis factor-α, interleukin-6. Based on these results, we propose that N7P can be used as a potent antiinflammatory agent.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.190.2-191
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• 2003

Production of prostaglandins involved in renal salt and water homeostasis is modulated by regulated expression of the inducible form of cyclooxygenase-2 (COX-2) at restricted sites in the rat kidney. COX-2 expression in the kidney is regulated by dietary salt intake, but the mechanism of its action is not fully understood. We have previously that high salt regulates COX-2 expression in rat kidney. (omitted)

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.135-135
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• 2002

Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in response to a variety of cytokines and other proinflammatory stimuli. It has been known that aberrant up-regulation of COX-2 is associated with resistance to apoptosis.(omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3447-3450
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• 2015

Objective: To explore the sensitivity of gastric cancer cells to chemotherapy drugs in elderly patients and its correlation with cyclooxygenase-2 (COX-2) expression in cancer tissue. Materials and Methods: Forty-three elderly patients with gastric cancer (observation group) and 31 young patients with gastrointestinal tumors (control group) who were all diagnosed by pathology and underwent surgery in the 89th Hospital of Chinese People's Liberation Army were selected. Drug sensitivity testing of tumor cells in primary culture was carried out in both groups using a methyl thiazolyl tetrazolium (MTT) method, and the expression of COX-2 and the factors related to multi-drug resistance (MDR) in cancer tissue were assessed by immunohistochemistry. Results: The inhibition rates (IR) of vincristine (VCR), 5-fluorouracil (5-FU), oxaliplatin (L-OHP), mitomycin (MMC) and epirubicin (eADM) on tumor cells in the observation group were dramatically lower than in the control group, with statistical significance (P<0.05 or P<0.01). The positive rates of COX-2, glutathione s-transferase-${\pi}$ (GST-${\pi}$) and P glycoprotein (P-gp) expression in cancer tissue in the observation group were all higher than in control group (P<0.05), while that of DNA topoisomerase $II{\alpha}$ ($TopoII{\alpha}$) expression lower than in the control group (P<0.01). In the observation group, COX-2 expression in cancer tissue had a significantly-positive correlation with GST-${\pi}$ and P-gp (r=0.855, P=0.000; r=0.240, P=0.026), but a negative correlation with $TopoII{\alpha}$ (r=-0.328, P=0.002). In the control group, COX-2 expression in cancer tissue was only correlated with P-gp positively (r=0.320, P=0.011). Bivariate correlation analysis displayed that COX-2 expression in cancer tissue in the observation group had a significantly-negative correlation with the IRs of 5-FU, L-OHP, paclitaxel (PTX) and eADM in tumor cells (r=-0.723, P=0.000; r=-0.570, P=0.000; r=-0.919, P=0.000; r=-0.781, P=0.000), but with hydroxycamptothecine (HCPT), VCR and 5-FU in the control group (r=-0.915, P=0.000; r=-0.890, P=0.000; r=-0.949, P=0.000). Conclusions: Gastric cancer cells in elderly patients feature stronger MDR, which may be related to high COX-2 expression.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.154-155
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• 2001

Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in response to a variety of proinflammatory agents and cytokines. COX-2 expression has been shown to be elevated in several different types of human cancer. The presence of oncogenic ras has been associated with constitutive induction of COX-2 in certain H-ras transformed cells, and COX-2 overexpression confers resistance to apoptosis.(omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.244.1-244.1
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• 2002

Cyclooxygenase-2 ( COX-2 ) is an inducible enzyme which produces prostanoids by various stimuli. Overexpression of COX-2 in many tumor types indicates its association with tumor progression, which has been a promising target for chemoprevention and chemomodulation. We studied conc- and time-dependency of COX-2 inhibition, growth inhibition, and cell cycle arrest induced by celecoxib, a selective COX-2 inhibitor, in human non-small cell lung cancer (NSCLC) A549 cells. (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.245.1-245.1
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• 2002

It has been known that resveratrol, a phytoalexin present in grapes mainly, has antioxidant. anti-inflammatory, and cancer chemopreventive activity. One mechanism of its anti-inflammation and cancer prevention is considered to modulate cyclooxygense-2 (COX-2) activity. Since COX-2 plays an important role in inflammation and carcinogenesis, the potential COX-2 inhibitors have been considered as anti-inflammatory or cancer chemopreventive agents. (omitted)