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.
【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 observe the effect of panretinal photocoagulation (PRP) on the expression of cyclooxygenase-2 (COX-2), vascular endothelial cell growth factor (VEGF) in epiretinal membrane of proliferative diabetic retinopathy (PDR). Methods Atotal of 35 patients (35 eyes) with PDR and underwent plana vitrectomy were enrolled in this study. The patients were divided into non-PRP group (19 patients, 19 eyes) and PRP group (16 patients, 16 eyes) depends on if they had received PRP before surgery. The epiretinal membranes stripped during operation were collected for pathological examination. The histopathological features was observed by haematoxylin and eosin stain. The expression of CD34, COX-2 and VEGF, and microvessel density (MVD) were measured by immunohistochemistry method. Results Many new dispersed capillary blood vessels were found in the thick epiretinal membranes of non-PRP group, while scattered small blood vessels were found in the relatively thin epiretinal membranes of PRP group. MVD value was (7.42±1.39) in the non-PRP group and (4.56±1.22) in the PRP group, which was lower than the non-PRP group (t=6.41, P<0.01). The expression of CD34, COX-2 and VEGF in the tissues of epiretinal membrane in PRP group were obviously lower than the non-PRP group (t=6.147, 5.944, 7.445; P<0.01). Conclusion PRP can effectively inhibit the expression of COX-2 and VEGF in epiretinal membrane of PRP patients.
Objective To investigate the expression of COX-2 in human cervical cancer and explore their relationship between the COX-2 expression and the clinicopathologic characteristic of cervical cancer. Methods The published studies were searched in the CBMdisc (1979 to 2009), CNKI (1979 to 2009), VIP (1989 to 2009) and WANFANG Database (1982 to 2009), and other relevant journals were also hand searched, 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 9 studies were recruited. As for the positive rate of COX-2 expression, significant differences was tested between cervical cancer vs. normal cervical tissues, lymph node metastasi vs. non-lymph node metastasi, clinical stages I-II vs. clinical stages III-IV, cell differentiation G1 vs. cell differentiation G2-G3 and cervical squamous cell carcinoma vs. adenocarcinoma with OR (95%CI) at 28.03 (9.53 to 82.50), 5.16 (3.36 to 7.93), 0.53 (0.33 to 0.84), 3.11 (1.86 to 5.22) and 5.00 (2.68 to 9.35) respectively. Conclusions According to the domestic evidence, higher COX-2 expression might be associated with cervical cancer. However, more high quality case-control studies are expected for further study.
【Abstract】Objective To investigate the relationship of expressions of cylooxygenase-2 (COX-2) and hypoxia-inducible factor-1α (HIF-1α) in hepatocelluar carcinoma (HCC) and the possible antineoplastic mechanism of selective COX-2 inhibitor. Methods The expressions of COX-2 and HIF-1α in 53 cases of HCC tissues were detected immunohistochemically. Western blot was employed to evaluate the effects of variant concentration of COX-2 inhibitor meloxicam on expression of HIF-1α in Cobaltchloridestimulated SMMC-7721 cell. ResultsOf 53 tumor tissues, the expression of COX-2 was 22/53 (41.5%) bly positive stained, 11/53 (20.8%) positive stained, and 20/53 (37.7%) negative stained. Meanwhile the expression of HIF-1α was 18/53 （34.0%） bly positive stained, 18/53 （34.0%）positive stained, 17/53（32.1%） negative stained. The expression of COX-2 was correlated positively with HIF-1α in HCC （r=0.440, P＜0.01）. The expression of HIF-1α increased sharply from 0.185±0.057 (no Cobaltchloride-stimulated) to 1.011±0.131 (Cobaltchloride-stimulated), and meloxicam could inhibit the expression of HIF-1α at either condition (P＜0.05). ConclusionMeloxicam could inhibit the expression of HIF-1α in a concentration-dependent manner in the Cobaltchloridestimulated SMMC-7721 cell. The antineoplastic activity of selective COX-2 inhibitor was possibly, at least in part, mediated by HIF-1α.
Objective To observe the effect of celecoxib on the expression vascular endothelial growth factors (VEGF) in diabetic rats. Methods Thirty-six wistar rats were used to establish the diabetic models by intraperitoneal injection with streptozotocin. The diabetic rats were divided into 2 groups: diabetic group (n=18) and celecoxib group (n=18). Celecoxib (50 mg/kg) was administered orally to the rats in celecoxib group and the physiological saline with the same volume was given orally to the rats in diabetic group. Eighteen else rats were in normal control group. All of the rats were executed 3 months later. The expression of VEGF protein was detected by immunohistochemistry method. Reverse transcription-polymerase chain reaction（RT-PCR） analysis was used to examine the expression of retinal VEGF mRNA and cyclooxygenase-2 mRNA. Results Lower positive expression of VEGF mRNA and cyclooxygenase-2 mRNA, weakly positive action of immunohistochemistry of VEGF, and lower expression of VEGF protein were detected in normal control group; in the diabetic group, the expression of VEGF mRNA and cyclooxygenase-2 mRNA increased obviously comparing with which in the control group (Plt;0.05), and the bly positive action of immunohistochemistry of VEGF and increased expression of VEGF protein were detected (Plt;0.01); in celecoxib group, the expression of VEGF mRNA was lower than that in the diabetic group (Plt;0.05), the expression of cyclooxygenase-2 mRNA didnprime;t decrease much (Pgt;0.05), the positive action of immunohistochemistry of VEGF decreased, and the expression of VEGF protein decreased (Plt;0.01). Conclusion By inhibiting the activation of cyclooxygenase-2, celecoxib can inhibit the expression of retinal VEGF mRNA and protein in diabetic rats induced by streptozotocin. (Chin J Ocul Fundus Dis,2007,23:265-268)
ObjectiveTo investigate the expression of keratinocyte growth factor (KGF) and cyclooxygen-ase-2 (COX-2) protein and microvessel density (MVD), and to explore their function and mechanism in the multistep process of gastric cancer. MethodsThe expressions of KGF and COX-2 protein in 64 samples of gastric cancer and 30 cases of normal gastric mucosa tissues were detected by immunohistochemistry. The MVD was detected by staining the endothelial cells in microvessles using anti-CD34 antibody. ResultsThe positive rate of KGF and COX-2 protein expression in gastric cancer were 65.6% (42/64) and 79.7% (51/64), respectively, which was significantly higher than that in normal gastric mucosa tissues 〔(23.3%, 7/30), P=0.046; (13.3%, 4/30), P=0.008〕. The MVD of gastric cancer was 31.8±8.0, which was significantly higher than that of normal gastric mucosa tissues (14.3±6.1), P=0.000. The MVD in gastric cancer with coexpressive KGF and COX-2 protein was 35.9±5.7, which was significant higher than that with non-coexpressive KGF and COX-2 protein (25.7±7.0), P=0.000. Both the expression of KGF and COX-2 protein were related to the invasion of serosa, lymph node metastasis and TNM staging (Plt;0.05, Plt;0.01). The MVD of gastric cancer tissues was related to lymph node metastasis and TNM staging (Plt;0.05), but unrelated to patient’s age, gender, and differentiation of tumor (Pgt;0.05). The co-expression of KGF and COX-2 protein was frequently found in patients with deeper invasion of serosa, lymph node metastasis, and higher TNM staging (Plt;0.05), but which was not associated withpatient’sage, gender, and differentiation of tumor (Pgt;0.05). The expression of KGF protein was positively correlated to the expression of COX-2 protein (r=0.610, P=0.000). There was positive correlation between MVD and the expression of KGF (r=0.675, P=0.000) and COX-2 protein (r=0.657, P=0.000) in gastric cancer, respectively. ConclusionKGF and COX-2 highly expressed by gastric cancer, which may be involved in the invasion and metastasis of gastric cancer by synergisticly promoting the angiogenesis.