• The Journal of the Korean Society for Microbiology
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• v.34 no.5
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• pp.479-489
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• 1999

Invasion of enteric bacteria, such as Salmonella and invasive E. coli, into intestinal epithelial cells induces proinflammatory gene responses and finally epithelial cell apoptosis. In this study, we asked whether invasive bacterial infection of human intestinal epithelial cells could upregulate cyclooxygenase-2 (COX-2) gene expression and whether increased COX-2 expression could influence intestinal epithelial cell apoptosis. Expression of COX-2 mRNA and prostaglandin (PG) $E_2$ production were upregulated in HT-29 colon epithelial cells which were infected with S. dublin or invasive E. coli, as examined by quantitative RT-PCR and radioimmunoassay. Inhibition of COX-2 expression and $PGE_2$ production using NS-398, a specific COX-2 inhibitor, showed a significant increase of epithelial cell apoptosis and caspase-3 activation in HT-29 cells infected with invasive bacteria. However, the addition of valerylsalicylate, a specific COX-1 inhibitor, did not change apoptosis in S. dublin-infected HT-29 cells. These results suggest that up regulated COX-2 expression and $PGE_2$ production in response to invasive bacterial infection could contribute to host defense by inhibiting apoptosis of intestinal epithelial cells.

• Journal of Acupuncture Research
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• v.23 no.2
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• pp.91-102
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• 2006

Objectives : Ulmus davidiana Planch (UD) has long been known to have anti-inflammatory and protective effects on damaged tissue, inflammation and bone among other functions. Methods : This study was undertaken to address whether the water extract of the bark of UD could modulate proliferation of mouse osteoclasts in vitro and to investigate its effect on cyclooxygenase-2 (COX-2), which converts arachidonic acid to prostaglandin E2 (PGE2) and is highly expressed in osteoclasts. Mouse osteoclasts were tested in vitro for growth inhibition, proliferation cell nuclear antigen expression, and COX-2 activity and expression after treatment with UD extract. Results : Its effects were compared with those of indomethacin (a nonselective COX inhibitor) and celecoxib (a selective COX-2 inhibitor) by Cell viability assay, Cell cycle analysis, Immunohistochemical analysis of PCNA expression, Western blot analysis and PGE2 Enzyme immunoassay (EIA). UD demonstrated a strong growth inhibitory action in both tested osteoclasts cells. The IC50s were $10\;{\mu}g/ml$ for UD, $6\;{\mu}M$ for celecoxib and $42\;{\mu}M$ for indomethacin. UD, as well as celecoxib and indomethacin, suppressed proliferation cell nuclear antigen expression and PGE2 synthesis in osteoclasts. UD inhibited COX-2 expression, whereas celecoxib inhibited COX-2 activity directly. Conclusion : UD selectively and effectively inhibits osteoclasts cell growth in vitro. Inhibitory action of PGE2 synthesis via suppression of COX-2 expression may be responsible for its anti-inflammatory activity.

• Animal cells and systems
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• v.16 no.4
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• pp.274-279
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• 2012

Thymoquinone (TQ), a drug extracted from the black seeds of Nigella sativa, has been shown to exhibit anti-inflammatory, anti-oxidant, and anti-neoplastic effects in numerous cancer cells. The effects of TQ on cyclooxygenase-2 (COX-2) expression and prostaglandin $E_2$ ($PGE_2$) production in MDA-MB-231, however, remain poorly understood. Western blot analysis and immunofluorescence staining were performed to study the expression levels of inflammation regulatory proteins in MDA-MB-231. $PGE_2$ assay was conducted to explore the TQ-induced production of $PGE_2$. In this study, we investigated the effects of TQ on COX-2 expression and $PGE_2$ production in MDA-MB-231. TQ significantly induced COX-2 expression and increased $PGE_2$ production in a dose-dependent manner, as determined by a Western blot analysis and $PGE_2$ assay. Furthermore, the activation of Akt and p38 kinase, respectively, was up-regulated in TQ treated cells. Inhibition of p38 kinase with SB203580 and PI3kinase (PI3K) with LY294002 abolished TQ-caused COX-2 expression and decreased $PGE_2$ production. These results collectively demonstrate that TQ effectively modulates COX-2 expression and $PGE_2$ production via PI3K and p38 kinase pathways in the human breast cancer cell line MDA-MB-231.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2979-2984
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• 2012

Recent studies have indicated a link between levels of cyclooxygenase-2 (COX-2) and development of the multidrug resistance (MDR) phenotype. The ATP-binding cassette sub-family G member 2 (ABCG2) is a major MDR-related transporter protein that is frequently overexpressed in cancer patients. In this study, we aimed to evaluate any positive correlation between COX-2 and ABCG2 gene expression using the COX-2 inducer 12-O-tetradecanoylphorbol-13-acetate (TPA) in human breast cancer cell lines. ABCG2 mRNA and protein expression was studied using real-time RT-PCR and flow cytometry, respectively. A significant increase of COX-2 mRNA expression (up to 11-fold by 4 h) was induced by TPA in MDA-MB-231 cells, this induction effect being lower in MCF-7 cells. TPA caused a considerable increase up to 9-fold in ABCG2 mRNA expression in parental MCF-7 cells, while it caused a small enhancement in ABCG2 expression up to 67 % by 4 h followed by a time-dependent decrease in ABCG2 mRNA expression in MDA-MB-231 cells. TPA treatment resulted in a slight increase of ABCG2 protein expression in MCF-7 cells, while a time-dependent decrease in ABCG2 protein expression was occurred in MDA-MB-231 cells. In conclusion, based on the observed effects of TPA in MDA-Mb-231 cells, it is proposed that TPA up-regulates ABCG2 expression in the drug sensitive MCF-7 breast cancer cell line through COX-2 unrelated pathways.

• Tuberculosis and Respiratory Diseases
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• v.63 no.1
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• pp.31-41
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• 2007

Background: In pathogenesis and prognosis of lung cancer, significance of enormous types of genetic expression were very compounding and undetermined. We performed this study to search association between clinical characteristics and expression of COX-2, MMP-9 and p53 in non-small cell lung cancer. Methods: Ninety-one patients with adenocarcinoma or squamous cell carcinoma were enrolled. We had searched clinical data retrospectively and performed immunohistochemical staining for COX-2, MMP-9 and p53. We had analyzed significance of these three genes in clinical features and prognosis for survival. Results: 1) In squamous cell carcinoma, male was predominant and was significantly correlated with smoking. 2) Major prognostic determinants for overall survival were curative resection. 3) Expression of COX-2 was more frequent in adenocarcinoma than in squamous cell carcinoma. 4) Negative staining of COX-2, MMP-9 and p53 was more frequent in squamous cell carcinoma than adenocarcinoma. 5) Survival duration was longer in the group with positive expression of p53 and negative for COX-2 and MMP-9 (median duration of survival = 165.6 weeks) than groups with the other expressional patterns. 6) Significant correlation was found between expression of MMP-9 and COX-2. In squamous cell carcinoma, expression of MMP-9, COX-2 and mutant p53 were mutually correlated. 7) COX-2 expression was significant prognostic factor for survival in resected cancer group. In unresected inoperable non-small cell lung cancer group, MMP-9 was statistically significant prognostic factor for overall survival. Conclusion: COX-2 and MMP-9 might have some roles for progression or prognosis in some selected patients with non-small cell lung cancer. COX-2 and MMP-9 may have some roles for disease progression or prognosis in selected patients with NSCLC.

• Animal cells and systems
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• v.16 no.5
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• pp.366-375
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• 2012

Gallotannin (GT) is derived from plant poly phenol and is associated with biological actions in a wide range of cells. In this study, we evaluated the effect of GTon apoptosis and cyclooxygenase-2 (COX-2) expression and attempted to shed light on the mechanism of action in A549 human lung carcinoma cells. We found that GT dramatically induced apoptosis as demonstrated by expression of p53 and active caspase-3 via western blot analysis and fragmented DNA as detected by DNA fragmentation and DAPI staining. We also observed that GT significantly causes COX-2 expression in a dose-dependent manner determined by western blot analysis. Phosphorylation of Akt and p38 was considerably increased by GT in A549 human lung carcinoma cells. Inhibition of Akt and p38kinase with LY294002 or SB203580 suppressed GT-induced apoptosis and COX-2 expression. Furthermore, we have shown that prevention of COX-2 with NS398 or indomethacin does not any effects on apoptosis induced by GT. Taken together, our present results suggest that GT regulates apoptosis and COX-2 expression through Akt and p38kinase pathway in A549, human lung carcinoma cells.

• Journal of dental hygiene science
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• v.15 no.6
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• pp.753-760
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• 2015

Although nuclear factor of activated T cell (NFAT) plays a key role in inflammation, its anti-inflammatory effects and mechanism of action in periodontitis are still unknown. This study aimed to identify the effects of NFAT on the proinflammatory mediators activated by lipopolysaccharide (LPS) plus nicotine stimulation in human periodontal ligament cells (hPDLCs). The production of nitric oxide (NO) and prostaglandin $E_2(PGE_2)$ was evaluated using Griess reagent and an enzyme immunoassay, respectively. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and NFAT proteins was evaluated by Western blot analysis. LPS plus nicotine synergistically induced the production of NO and $PGE_2$ and increased the protein expression of iNOS, COX-2 and NFAT. Treatment with an NFAT inhibitor blocked the LPS plus nicotine-stimulated NO and $PGE_2$ release as well as the expression of iNOS and COX-2. Our data suggest that the LPS plus nicotine-induced inflammatory effects on hPDLCs may act through a novel mechanism involving the action of NFAT. Thus, NFAT may provide a potential therapeutic target for the treatment of periodontal disease associated with smoking and dental plaque.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.3
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• pp.231-240
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• 2007

It has been reported the higher incidence rate of gastric cancer in our country. Helicobacter pylori (H. pylori), that exhibited a higher infection rate among Korean people, has been known as a cofactor to cause cancer. Therefore, the aim of this study was to identify correlations among overexpressions of COX-2 (Cyclooxygenase-2) gene, p53 mutation and cell proliferation index related to H. pylori. Taking 28 cases of gastric cancer with H. pylori detection, immunohistochemical staining for COX-2, p53 and Ki-67 were performed. In the H. pylori positive group, the well differentiated type and diffuse type of gastric cancer were distributed in larger area and the expression rate of COX-2 was revealed high. The H. pylori negative group showed higher p53 expression than that of the positive group. However, the statistical correlation between H. pylori and histopathological factors was not observed. The significantly higher expression of COX-2 had were observed in both well differentiated type and the intestinal type of gastric cancer. Although there were no statistical significances, this showed a higher inclination of manifest in the early gastric cancer. p53 exhibited a higher tendency of expression in the well differentiated, moderately differentiated and the intestinal type of gastric cancers including the early gastric cancer. Ki-67 was expressed in a significantly higher fashion along with the increase of age. In addition, it was significantly expressed in well differentiated type and intestinal type of gastric cancer. Therefore, these results suggest that H. pylori, COX-2, p53, and Ki-67 influences on the new occurrence of gastric cancer and its development procedures. In the future, the more researches would be required to focus on a larger category relative to gene expressions in gastric cancer.

• The Journal of Korean Medicine
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• v.41 no.4
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• pp.12-26
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• 2020

Objectives: The aim of this study is to investigate the mechanisms involved in the anti-inflammatory and anti-tumor effects of Rhus verniciflua Stokes (RVS) on PMA-differentiated human monocytic leukemia THP-1 cells. Methods: Cells were treated with various concentrations of RVS decoction (0-300㎍/ml) for 24, 48, and 72h. Cell viability was evaluated by MTS/PMS assay. The expressions of MMP-2, MMP-9, TIMP-1, TIMP-2, iNOS and COX-2 mRNA and proteins were measured using RT-PCR and western blotting, respectively. Results: RVS suppressed expression of MMP-2 and MMP-9 mRNA. It also down-regulated iNOS and COX-2 mRNA and protein expression. RVS inhibited NF-𝜅B p65 activity and the phosphorylation of Akt and MAPK (ERK and p38 MAPK). Instead, the phosphorylation of JNK is increased at a very low concentration but decreased at higher concentrations. Conclusion: RVS is regarded to inhibit the expression of MMP and TIMP as well as iNOS and COX-2 gene expression via directly inhibiting the activation of NF-𝜅B and phosphorylation of MAPK pathway in THP-1 cells. This suggests RVS have potential to be used as a therapeutic agent for acute myeloid leukemia (AML).

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4453-4458
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• 2012

Angiogenesis plays a significant role in colorectal cancer (CRC) and cyclooxygenase-2 (COX-2) appears to be involved with multiple aspects of CRC angiogenesis. Our aim was to investigate the inhibitory effects of Tan II-A (Tanshinone II-A, Tan II-A) on tumor growth in mice, as well as alteration of expression of COX-2 and VEGF in CRC. We established the mice xenograft model of C26 CRC cell line, and injected 0.5, 1, 2mg/kg of Tan II-A and 1mg/kg of 5-FU in respectively in vivo. Then, we assayed tumor weight and volume, and evaluated microvascular density and expression of VEGF. COX-2 promoter and COX-2 plasmids were transfected into HCT-116 cells, followed by detection of COX-2 promoter activity by chemiluminescence, and detection of COX-2 mRNA expression by fluorescence quantitative PCR. Taken together, the results showed Tan II-A could inhibit tumor growth and suppress the VEGF level in vivo. HCT-116 cell experiments showed marked inhibitory effects of Tan II-A on COX-2 and VEGF in a dose-dependent manner. The results indicate that Tan II-A can effectively inhibit tumor growth and angiogenesis of human colorectal cancer via inhibiting the expression level of COX-2 and VEGF.