Objective To summarize the research progress in antitumor mechanism of non-steroidal anti-inflam-matory drugs. Methods The domestic and international published literatures about antitumor mechanism of non-steroidal anti-inflammatory drugs in recent years were reviewed. Results The antitumor mechanism of non-steroidal anti-inflam-matory drugs was multistrata and multidigit. Conclusion Non-steroidal anti-inflammatory drugs can be used to prevent the development of colorectal cancer and also be a adjuvant therapy after radical operation for colorectal cancer.
Objective To investigate the effect of inducible nitric oxide synth ase (iNOS) or cyclooxygenase－2 (COX－2) on retinal neovascularization and its possible mechanism in oxygen－induced retinopathy （OIR） mouse model. Methods Retinal neovascularization was induced by oxygen with different concentration. The expression of iNOS, COX－2, matrix metalloproteinases 2 (MMP－2) and vascular end othelial growth factor (VEGF) in the retinae of experimental animals were analyzed by immunohistochemistry, realtime polymerase chain reaction and western blotting technologies. Results The inhibition of COX－2 or iNOS obviously attenuated retinal neovascularization and decreased the expression of VEGF and MMP－2. The iNOS inhibition decreased COX－2 expression, and vice versa. Conclusions COX－2 and iNOS may play a role in retinal neovascularization in OIR mouse model, which may act by regulating the expression of VEGF and MMP－2.
ObjectiveTo observe the effect of lentivirus-mediated cyclooxygenase 2 (COX-2) and Aggrecanase-1 silencing and insulin-like growth factor 1 (IGF-1) in BMSCs after injecting into the knee joint cavity in cynomolgus monkeys with knee osteoarthritis (OA). MethodsBMSCs were isolated from the bone marrow of 10 donors. The lentivirus vector expressing genes of COX-2, Aggrecanase-1, and IGF-1 were constructed, and transfected into the third generation human BMSCs at 40 multiplicity of infection (virus group); BMSCs transfected with lentivirus-empty vector served as blank-virus group. The growth status and number of BMSCs were observed under inverted phase contrast microscope, and normal BMSCs were used as normal control group. At 1 week after transfected, the mRNA expressions of COX-2, Aggrecanase-1, and IGF-1 were detected with RT-PCR. Nine 3-year-old cynomolgus monkeys were selected to establish the OA model according to Hulth modeling method, and were randomly divided into 3 groups (n=3). At 6 weeks after remodeling, the right knee joint cavity was injected accordingly with 1 mL BMSCs (about 1×107 cells) in virus group and blank-virus group, with 1 mL of normal saline in the blank control group; the left knee served as normal controls. The general condition was observed after injection; at 1, 4, and 6 weeks, the concentrations of prostaglandin E2 (PGE2), IL-1, Aggrecanase-1, and IGF-1 of double knee liquid were detected with ELISA; at 6 weeks, MRI, general observation, histology method, and immunohistochemistry method were used to detect the knee cartilage changes and the expressions of COX-2, Aggrecanase-1, and IGF-1 were measured with RT-PCR. ResultsNo significant difference was found in cell morphology and growth curve between 2 groups after transfection. By RT-PCR, COX-2, and Aggrecanase-1 expressions were significantly reduced, IGF-1 expression was significantly increased in virus group when compared with normal control group and the blank-virus group (P < 0.05). All monkeys survived to the end of the experiment after injection. When compared with blank-virus group and blank control group, the concentrations of PGE2, Aggrecanase-1, and IL-1 significantly decreased and the concentration of IGF-1 significantly increased in the virus group (P < 0.05), but the indicators in 3 groups were significantly higher than those in the normal control group (P < 0.05). MRI showed that abnormal articular surface with high density could be found in virus group, blank-virus group, and blank control group, while the virus group had the minimum area. Gross observation and histological observation showed that the cartilage morphology of virus group, blank-virus group, and blank control group was accordance with early OA articular cartilage changes, but virus group was better than blank-virus group and blank control group in repair degree, whose improved Pineda score was significantly lower (P < 0.05). Immunohistochemical staining showed that the virus group had deeper dyeing with occasional brown particles and more chondrocytes than blank-virus group and blank control group. By RT-PCR, COX-2 and Aggrecanase-1 mRNA expressions of cartilage in virus group were significantly decreased, and IGF-1 expression was significantly increased when compared with blank control group and the blank-virus group (P < 0.05). ConclusionLentivirus-mediated multi-genes co-transfection in BMSCs can inhibit the expressions of COX-2 mRNA and Aggrecanase-1 mRNA, and enhance the IGF-1 mRNA expression, which decreases the concentration of inflammatory factors, and protects the joint cartilage effectively.
【Abstract】Objective To investigate the effects of selective cyclooxygenase-2 (COX-2) inhibitor nimesulide on the proliferation of colon adenocarcinoma cells in vitro and the expression of matrix metalloproteinase-2 (MMP-2). Methods The human colon cancer cell lines HT-29 and HCT-116 were employed in the study, grouped as nimesulide group, DMSO control group and blank control group. After treatment with nimesulide, the inhibitory effect of nimesulide on the proliferation of cancer cells was quantified by MTT assay, and the expression of MMP-2 in the cells was detected by quantitative zymography. Results Nimesulide inhibited the proliferation of HT-29 and HCT-116 cells in time and dosedependent manners. The inhibitory effect on HT-29 cells was ber than that on HCT-116 cells. Nimesulide downregulated the MMP-2 expression in HT-29 cells, whereas the expression in HCT-116 cells remained unchanged. Conclusion Nimesulide can obviously inhibit the growth of colon cancer HT-29 cells with positive COX-2 protein, suggesting that nimesulide may downregulate the expression of MMP-2 by inhibiting the activity of COX-2.
ObjectiveTo investigate the expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in human pancreatic adenocarcinoma and their correlation with clinicobiological behavior.MethodsThe expression of COX-2 and VEGF in 51 cases of human pancreatic ductal adenocarcinoma were detected with immunohistochemistry of Envision.ResultsExpression of COX-2 and VEGF in pancreatic ductal adenocarcinoma were 74.5% and 68.6%, respectively; no expression of COX-2 and VEGF in adjacent normal tissue was detected. Both COX-2 and VEGF expression in clinical stage Ⅲ-Ⅳ were much higher than those in clinical stage Ⅰ-Ⅱ, and also higher in positive group of lymph node metastasis than in negative group as well (Plt;0.05). None of them had relation with histological grades, age, sex, tumor size and location. The expression of COX-2 was closely correlated with VEGF (r=0.411, Plt;0.01).ConclusionCOX-2 and VEGF may play a pivotal role in tumorigenesis and tumor progression in pancreatic cancer, they may provide new targets for therapy of pancreatic cancer.
Objective To investigate the expression and clinical significance of cyclooxygenase-2 (COX-2) in human breast cancer with meta-analyses. Methods The published studies were searched in the CBM, CNKI, VIP and WanFang databases, and other relevant journals were also handsearched to identify all the relevant case-control trials. The quality of the included studies was assessed. The Cochrane Collaboration’s software RevMan 4.2.10 was used to test the heterogeneity, overall effect and publication bias of the combined studies. Results A total of 8 studies were recruited. As for the positive rate of COX-2 expression, significant differences were tested between breast cancer vs. normal breast tissues, cell differentiation G1 vs. cell differentiation G2-G3 with OR (95%CI) at 16.36 (9.18, 29.15) and 0.34 (0.18, 0.63), respectively. No significant difference was tested between lymph node metastasi vs. non-lymph node metastasi, clinical stages I-II vs. clinical stages III-IV with OR (95%CI) at 1.36 (0.61, 3.03) and 0.61 (0.34, 1.10), respectively. Conclusion According to the domestic evidence, COX-2 may be participated the whole course of carcinogenesis of breast cancer, but is not the absolute factor for estimating the survival rate of the patients with breast cancer, and more high-quality studies are expected for further study.
Objective To detect the expressions of epidermal growth factor receptor (EGFR), epidermal growth factor receptor-2 (C-erbB-2), vascular endothelial growth factor (VEGF) and cyclooxgenase-2 (COX-2) in gastric cancer tissues, and to analyze the relationship among them and the clinicopathologic factors of gastric cancer. Methods The SP immunohistochemical stain was used to detect EGFR, C-erbB-2, VEGF and COX-2 protein expressions in sample of 68 gastric cancer tissues. And their corresponding clinical data were analyzed retrospectively. Results The expression rates of EGFR, C-erbB-2, VEGF and COX-2 protein in gastric cancer tissue were 38.2% (26/68), 42.6% (29/68), 52.9% (36/68) and 60.3% (41/68) corresponding. An obvious increasing tendency as the differentiation of the cancer degraded, invasion depth deepened, lymphatic metastasis occurred and TNM stage upgraded was showed by the positive expression rates of them （P＜0.05，P＜0.01）; but there was no correlation with the patient’s sex, age, tumour site and size （Pgt;0.05）. There was a stable positive correlation among EGFR, C-erbB-2, VEGF and COX-2 expressions in gastric cancer tissue, respectively （P＜0.05）. Conclusion EGFR, C-erbB-2, VEGF and COX-2 expressions participate in the development, invasion and metastasis process of gastric cancer. Joint detection of them can be looked as an important symbol for judging the prognosis of gastric cancer and screening the high-risk metastasis patients, and guiding the molecular targeting therapy of gastric cancer.
ObjectiveTo explore the correlation between -765G/C polymorphism of cyclooxygenase-2 (COX-2) gene and the risk of ischemic stroke (IS). MethodsPubMed, CBM, The Cochrane Library (Issue 3, 2015), CNKI, CBM, VIP and WanFang Data were searched from inception to March 2015 to collect case-control or nested case-control studies about -765G/C polymorphism of COX-2 gene and the risk of IS. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.1 software and Stata 12.0 software. ResultsA total of 10 studies involving 2611 cases and 18589 controls were included. The results of meta-analysis showed that, there was no correlation between -765G/C polymorphism and the risk of IS (GC+CC vs. GG: OR=1.05, 95%CI 0.88 to 1.25, P=0.620; CC vs. GG+GC: OR=1.04, 95%CI 0.83 to 1.30, P=0.730; GC vs. GG: OR=1.04, 95%CI 0.87 to 1.25, P=0.630; CC vs. GG: OR=1.09, 95%CI 0.86 to 1.36, P=0.480; C vs. G: OR=1.03, 95%CI 0.89 to 1.20, P=0.700). Subgroup analysis results showed that, the COX-2 gene -765G/C polymorphism was a risk factor for IS in African-Americans (GC+CC vs. GG: OR=1.42, 95%CI 1.12 to 1.78, P=0.003; GC vs. GG: OR=1.39, 95%CI 1.09 to 1.78, P=0.008; CC vs. GG: OR=1.51, 95%CI 1.04 to 2.18, P=0.030; C vs. G: OR=1.27, 95%CI 1.08 to 1.51, P=0.004), but not in Asians and Caucasians. ConclusionCurrent evidence shows that -765G/C polymorphism of COX-2 gene may be a genetic risk factor for IS in African-Americans, but not in Asians and Caucasians. Due to the limited quantity and quality of the included studies, more high quality studies are needed to verify the above conclusion.
ObjectiveTo systemically evaluate the efficacy and safety of cyclooxygenase-2 (COX-2) signal pathway inhibition in treating advanced non-small cell lung cancer (NSCLC). MethodsA systematic literature search in PubMed, EMbase, Cochrane Library, ASCO databases, CNKI and Wanfang database was conducted to identify relevant randomized controlled trials (RCTs) from the time of database establishment to June 2015. RCTs of COX-2 inhibitors treating advanced NSCLC were included. We assessed the methodology quality of the included studies by using Jadad's scale, and performed this meta-analysis by using stata12.0 software. ResultsTwelve RCTs involving three different COX-2 inhibitors with a total of 1 828 patients were identified including 8 studies of high quality and 4 studies of low quality. We found that COX-2 signal pathway inhibition could significantly increase overall response rate at RR=1.27 with 95%CI1.10 to 1.46 (P=0.001). While our present data could not confirm the efficacy of COX-2 inhibitors in improving progression-free survival (PFS) at HR=0.93 with 95%CI0.81 to 1.08 (P=0.334), overall survival (OS) at HR=0.95 with 95%CI0.84 to 1.08 (P=0.461), or one-year survival rate at RR=1.08 with 95%CI0.90 to 1.24 (P=0.29). As for toxicities, only increased risk of thrombocytopenia at RR=1.28 with 95%CI 1.03 to 1.85 (P=0.03) was observed in the patients treated with COX-2 inhibitors. ConclusionCOX-2 signal pathway inhibition is effective in improving the overall response rate of the patients with advanced NSCLC, and is well tolerated. Whether COX-2 signal pathway inhibition is effective in improving long-term survival of the patients with advanced NSCLC still needs to be confirmed via further clinical trials.
Objective To investigate the expression of cyclooxygenase-2 (COX-2) in liver tissue of severe acute pancreatitis (SAP) rats. Methods A rat model of SAP was induced by retrograde infusion of 3.5% sodium taurocholate into the biliary-pancreatic duct. Eighty rats were randomly divided into SAP group and control group. The levels of serum amylase (AMY), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor (TNF) -α and ascites AMY were detected dynamically at 4 h, 8 h, 16 h and 24 h after operation. The pancreatic and liver injuries were observed by light microscope. The expression of COX-2 in liver tissue was measured by immunohistochemistry. Results Compared with the control group, the levels of serum AMY, ALT, AST, TNF-α and ascites AMY increased significantly at the time point of 4 h, 8 h, 16 h and 24 h (Plt;0.05). These changes were paralleled with the histopathological changes of pancreatic and liver tissue. The expression positive rates of COX-2 at the different time in the SAP group were higer than those of the control group (Plt;0.05). There was a significantly positive correlation between the expression of COX-2 and ALT (rs=0.949, P=0.039), AST (rs=0.972, P=0.016) and serum AMY (rs=0.944, P=0.041), respectively. Conclusion Overexpression of COX-2 may play an important role in liver injury during SAP.