• 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.

• Journal of Korean Neurosurgical Society
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• v.38 no.4
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• pp.287-292
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• 2005

Objective : Kainic acid[KA] enhances the expression of nitric oxide synthase, increases nitric oxide[NO], and thus evokes epileptic convulsion, which results in neuronal damage in the rat brain. NO may stimulate cyclooxygenase type-2 [COX-2] activity, thus producing seizure and neuronal injury, but it has also been reported that KA-induced seizure and neurodegeneration are aggravated on decreasing the COX-2 level. This study was undertaken to investigate whether the suppression of NO using the NOS inhibitor, N-nitro-L-arginine methyl ester[L-NAME], suppresses or enhances the activity of COX-2. Methods : Silver impregnation and COX-2 immunohistochemical staining were used to localize related pathophysiological processes in the rat forebrain following KA-induced epileptic convulsion and L-NAME pretreatment. Post-injection survival of the rat was 1, 2, 3days and 2months, respectively. Results : After the systemic administration of KA in rats, neurodegeneration increased with time in the cornu ammonis [CA] 3, CA 1 and amygdala, as confirmed by silver impregnation. On pretreating L-NAME, KA-induced neuronal degeneration decreased. COX-2 enzyme activities increased after KA injection in the dentate gyrus, CA 3, CA 1, amygdala and pyriform cortex, as determined by COX-2 staining. L-NAME pretreatment prior to KA-injection, caused COX-2 activities to increase compared with KA- injection only group by 1day and 2days survival time point. Conclusion : These results suggest that L-NAME has a neuroprotective effect on KA-induced neuronal damage, especially during the early stage of neurodegeneration.

• The korean journal of orthodontics
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• v.35 no.5 s.112
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• pp.351-360
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• 2005

This study aimed to investigate the effects of indomethacin on distribution and expression of COX-2 and IGF-1 in the mandibular condyle ofi growing dogs and to examine the number of chondroclasts around the mineralization zone indomethacin inhibits prostatlandin $E_2$ production in the tissue by inhibiting synthesis of cyclooxygenase 2. Prostaglandin $E_2$ stimulates insulin-like growth factor synthesis. Insulin-like growth factor stimulates growth of mandibular condylar cartilage. Eight mongrel dogs. aged 13-14 weeks, were divided into 4 groups. Group 1 and group 2 were administered indomethacin 2 mg/Kg/day orally two times a day for 7 days and 14 days respectively. Group 3 were administered indomethacin 8mg/Kg/day orally 2 times a day for 14 days, and 4he control group were administered a placebo. The mandibular condyle heads were sectioned in $5{\mu}m$ thickness The specimens were stained with H-E staining. COX-2 immunohistochemical staining and IGF-1 immunohistochemical staining and examined under microscope. After TRAP staining, the number of chondroclasts were calculated The observed results were as follows: Indomethacin inhibited expression and distribution of COX-2 and IGF-1 on the proliferative zone of condylar cartillage. Indomethacin decreased the number of chondroclastes on the mineralization zone by a time-dependent manner (P<0.05). Indomethacin inhibited expression and distribution of IGF-I by a dose and time-dependent manner. These results show that indomethacin inhibited expression and distribution of COX-2 and IGF-1 on the proliferative zone of condylar cartilage and decreased the number of chondroclasts and suggests that when indomethacin is administered for a long time, condyle growth could be delayed.

• The Journal of Korean Medicine
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• v.23 no.3
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• pp.188-199
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• 2002

Objectives : Banhasasim-tang has been clinically used to treat upper gastric intestinal discomfort. The object of this study is to examine the defense effect of Banhasasim-tang for acute duodenal injury of the mouse. Methods and Materials : Twenty-one rats were divided into 3 groups and treated as follows: the control group was untreated mice. The ADE group was acute duodenal-damage-elicited mice. The BST group was Banhasasim-tang treated mice before acute duodenal damage elicitation. The groups were examined with common morphology, paneth cells in intestinal crypt, absorptive cells and goblet cells in epithelium, cell division in mucose, COX-l as mucosal protector, COX-2 (which appears to play an important role in inflammation), IL-2R-inducing cellular immuno-chainreaction, and the distribution of apoptotic cells. Results : 1. Common morphology: the ADE group was observed with duodenal injury - loss of villi, infiltration of cells concerned to inflammation (lymphocytes, granular leukocytes) to submucosal layer - by hemorrhagic erosions, while the BST group was seen the same as normal in proportion to increasing treatment time before injury. 2. Histochemical change: the ADE group was observed with noticeable decreased distribution of absorptive cells with microvilli, acid mucin secreted goblet cell, neutral mucin secreted goblet cell, paneth cells compared to the normal group. The BST group was seen to have distribution of epithelium cells resembling normal in proportion to increasing treatment time before injury. 3. Imnunohistochemical change: the ADE group showed a change of factors leading to duodenal injury as reduce of cytokinesis, COX-1, increase of COX-2, IL-2R-. In contrast, the BST group tended to reduction of cytokinesis, COX-1, increase of COX-2, IL-2R- in proportion to increasing taking time before injury. 4. Apoptosis change: the ADE group showed increasing apoptosis cells, in contrast to the BST group which was the same as normal in proportion to increasing treatment time before injury. Conclusions : According to the above results, by increasing the defense system of mucosal epithelium, Banhasasim-tang is thought to effectively protect tissue against ulcers resulting from acute duodenal injury.

• Journal of Life Science
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• v.19 no.10
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• pp.1396-1402
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• 2009

Hizikia fusiforme is a kind of edible brown seaweed that grows mainly in the northwest Pacific including Korea, Japan and China, and has been widely used as food in Korea. Induction of cyclooxygenase-2 (COX-2) expression and prostaglandin $E_2$ ($PGE_2$) production is thought to have beneficial immunomodulatory effects in acute and chronic inflammatory disorders. In this study, we investigated the effects of extracts of H. fusiforme on the expression of COX-2 and production of $PGE_2$ in U937 human pre-monocytic cell models. In U937 cells stimulated with phorbol 12-myristate 13-acetate (PMA) to mimic inflammation, methanol extract of H. fusiforme (MEHF) and ethanol extract of H. fusiforme (EEHF), but not water extract of H. fusiforme (WEHF), inhibited PMA-induced expression of both COX-2 protein and mRNA, which was associated with inhibition of $PGE_2$ production. To investigate the mechanism by which MEHF and EEHF inhibit COX-2 gene expression and $PGE_2$ production, we examined the activation of nuclear factor-kappaB (NF-$\kappa$B) in U937 cells. Pre-treatment with MEHF and EEHF significantly attenuated the PMA-induced IkappaB degradation and prevented nuclear translocation of NF-$\kappa$B. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-inflammatory activity of H. fusiforme.

• IMMUNE NETWORK
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• v.13 no.2
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• pp.75-79
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• 2013

Evidence for immunoregulatory roles of prostaglandins (PGs) is accumulating. Since our observation of PG production by human follicular dendritic cells (FDCs), we investigated the regulatory mechanism of PG production in FDC and attempted to understand the functions of released PGs in the responses of adjacent lymphocytes. Here, using FDC-like cells, HK cells, we analyzed protein expression alterations in cyclooxygenase-2 (COX-2) in the presence of IL-4 or histone deacetylase (HDAC) inhibitors. Both IL-4 and HDAC inhibitors suppressed COX-2 expression in dose-dependent manners. Their effect was specific to COX-2 and did not reach to COX-1 expression. Interestingly, HDAC inhibitors gave rise to an opposing effect on COX-2 expression in peripheral blood monocytes. Our results suggest that IL-4 may regulate COX-2 expression in FDCs by affecting chromatin remodeling and provide insight into the role of cellular interactions between T cells and FDC during the GC reaction. Given the growing interests in wide-spectrum HDAC inhibitors, the differential results on COX-2 expression in HK cells and monocytes raise cautions on their clinical use.

• The Journal of the Korean bone and joint tumor society
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• v.13 no.2
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• pp.105-112
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• 2007

Purpose: Recent studies have shown increased levels of cyclooxygenase-2 (COX-2) in various human malignancies to include various bone and soft tissue tumors. However, little is known with regard to COX-2 expression patterns in chondroid tumors. Materials and Methods: Immunohistochemistry assays were performed for COX-2 in enchondromas (n=10), chondroblastomas (n=11), chondromyxoid fibromas (n=5), conventional chondrosarcomas (n=17), clear cell chondrosarcomas (n=7), and mesenchymal chondrosarcomas (n=6). Results: Among the benign chondroid tumors, chondroblastomas revealed characteristic strong positivity in 6 of 11 cases(54.5%). All enchondromas and chondromyxoid fibromas were negative except in one case. In conventional chondrosarcomas, three cases(17.6%) were strongly reactive with COX-2 and all positive cases represented grade III chondrosarcomas. Clear cell chondrosarcomas were found to be focally positive in two cases(28.5%), while all mesenchymal chondrosarcomas were negative. Conclusions: These findings suggest that COX-2 overexpression in conventional chondrosarcoma may represent an advanced histologic grade. Interestingly, expression of COX-2 in chondroblastomas could be an important factor for inducing peritumoral inflammatory changes in these specific tumors.

• Korean Journal of Medicinal Crop Science
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• v.13 no.2
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• pp.75-79
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• 2005

Five coumarins, psoralen (1), scopoletin (2), isoimperatorin (4), (+)-marmesin (5) and xanthotoxin (6), three chromones, cimifugin (3), hamaudol (7) and sec-O-glucosylhamaudol (10), one sterol, daucosterol (8) and one aliphatic alcohol, galactitol (9) were isolated from the root of Peucedanum japonicum. Their chemical structures were identified by the physicochemical and spectroscopic data by comparing literature values. Among them, compounds 9 and 10 were isolated for the first time from this plant. The anti-inflammatory effects of isolated compounds were examined on cyclooxygenase (COX), compounds 1, 2 and 7 showed inhibitory activity on COX-1 with $IC_{50}$ values of 0.88, 0.27 and 0.30 mM, respectively. In the test for COX-2 activity, only compound 7 showed significant inhibitory activity with the $IC_{50}$ value of 0.57 mM. The other compounds exhibited weak inhibitory or no inhibitory activity.

• Journal of Gastric Cancer
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• v.9 no.3
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• pp.96-103
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• 2009

Purpose: Lymph node metastasis is an important factor in determining prognosis and therapeutic options for early gastric cancer (EGC) patients. Vascular endothelial growth factor (VEGF)-C and D are known as lymphangiogenic factors, and cyclooxygenase (COX)-2 is thought to play a role in lymph node metastasis in gastric carcinoma. This study was designed to determine whether the expression of VEGF-C, VEGF-D, and COX-2 is associated with clinicopathologic factors, especially lymph node metastasis in EGCs invading the submucosa. Materials and Methods: Tissue samples were obtained from 85 Patients undergoing standard gastrectomy with lymph node dissection between 1991 and 2007 in the Department of Surgery of Daejeon St. Mary's Hospital in Daejeon, Korea. All patients were diagnosed with gastric cancers and submucosal invasion. We examined the expression of VEGF-C, VEGF-D, and COX-2 using immunohistochemical methods. Results: Of the 85 patients, 16 (18.8%) had lymph node metastasis. VEGF-C, VEGF-D, and COX-2 were positively expressed in 34.1% (29/85), 22.3% (19/85), and 37.6% (32/85) of the patients. VEGF-C and COX-2 expression was significantly correlated with lymph node metastasis (P<0.05). A positive correlation existed between VEGF-C and COX-2 expression (P< 0.001). Conclusion: VEGF-C and COX-2 expression is associated with lymph node metastasis in gastric cancer with submucosal invasion. VEGF-C and COX-2 may thus be predictive markers for lymph node metastasis in EGC patients with submucosal invasion.

• Journal of Pharmacopuncture
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• v.6 no.2
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• pp.77-90
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• 2003

The purpose of this study was to investigate the effect of Bee Venom on the lipopolysaccharide(LPS), sodium nitroprusside(SNP), hydrogen peroxide($H_2O_2$)-induced expressions of cyclooxygenase-2(COX-2), p38, jun N-terminal Kinase(JNK) and extra-signal response kinase(ERK) in RAW 264.7 cells, a murine macrophage cell line. Method : The expressions of COX-2, p38, JNK and ERK were determined by western blotting with corresponding antibodies. Results : 1. The 0.5, 1 and $5\;{\mu}g/ml$ of bee venom inhibited significantly LPS and SNP-induced expression of COX-2 compared with control, respectively. The 0.5, 1 and $5\;{\mu}g/ml$ of bee venom inhibited insignificantly $H_2O_2$-induced expression of COX-2 compared with control, respectively. 2. The 0.5, 1 and $5\;{\mu}g/ml$ of bee venom inhibited significantly LPS, SNP and $H_2O_2$-induced expression of p38 compared with control, respectively. 3. The 1 and $5\;{\mu}g/ml$ of bee venom inhibited significantly SNP-induced expression of JNK compared with control, respectively. All of bee venom inhibited insignificantly LPS and $H_2O_2$-induced expression of JNK compared with control, respectively. 4. The $5\;{\mu}g/ml$ of bee venom inhibited significantly SNP-induced expression of ERK, the $0.5\;{\mu}g/ml$ of bee venom increased significantly $H_2O_2$-induced expression of ERK compared with control. The 0.5, 1 and $5\;{\mu}g/ml$ of bee venom inhibited insignificantly LPS-induced expression of ERK compared with control, respectively.