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Objective To analyze the influence of Guizhifuling capsule on serum vascular endothelial growth factor(VEGF) and matrix metalloproteinase-2 (MMP-2) in patients with endometriosis after operation.Methods According to digital table,100 patients with endometriosis after operation were randomly divided into the control group (50 cases) and the observation group (50 cases).The patients in the control group were treated through mifepristone,while the patients in the observation group were treated through Guizhifuling capsule.They were all treated for three months.VEGF and MMP-2 were detected before and after treatment.Results The total effective rate was 92％ in the observation group,which was significantly higher than 84％ in the control group (x2 =4.16,P ＜0.05).After treatment for three months,serum levels of VEGF and MMP-2 were both decreased in two groups (t =2.009,4.432,25.600,19.064,all P ＜0.01).Compared with the control group,the decrease of VEGF and MMP-2 in observation group were more significant (t =21.783,13.112,all P ＜ 0.05).Conclusion Guizhifuling capsule can improve the symptoms of patients with endometriosis by reducing the expression of VEGF and MMP-2.
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Objective To investigate the effects of the leflunomide active metabolite (A771726) on the expression of phorbol-12-myristate-13-acetate (PMA) -induced CD147, matrix metallo-proteinase (MMP)-2 and MMP-9 on THP-1 cells. Methods THP-1 cells were cultured in RPMI-1640 medium supplemented with 10％ fetal bovine serum. For all experiments, THP-1 cells were cultured at an initial density of 5×105/ml. Before A771726 treatment, cells were cultured with serum-free RPMI-1640 medium for 12 h, THP-1cells were co-cultured with PMA at three different concentrations of A771726 (5, 15 , 45 μg/ml) for 24 h.The mRNA expression of CD147, MMP-2 and MMP-9 was measured by real-time PCR. CD147 expression on the cells were evaluated by flow cytometric analysis. The activity of MMP-2 and MMP-9 were evaluated by gelatin zymography. Statistical differences among the groups were tested by one-way ANOVA or KruskalWallis test. Results The expression of CD147, MMP-2 and MMP-9 were upgraded by the PMA. The expression of CD147 on THP-1 cells was inhibited significantly by A771726 in a dose-dependent pattern (P＜0.01). The mean fluorescence intensity (MFI) of CD147 in positive control group was 109.5±3.8, the MFI in A771726 (5, 15, 45 μg/ml) group were 73.3±2.5, 64.5±2.3, 40.9±2.7, respectively. The expression of MMP-2, MMP-9 mRNA and the activity of MMP-2, MMP-9 in the supernatant was inhibited significantly by A771726 (P＜0.01). The expression of CD147 mRNA was not inhibited significantly by A771726 (P＞0.05).Conclusion Leflunomide active metabolite (A771726) can inhibit the expression of PMA-induced CD147,MMP-2 and MMP-9 on THP-1 Cells.
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Objective Studing the relationship among matrixmetal-loproteinnse2 (MMP2), the tissue inhibitors of metalloprotein-ase2 (TIMP2) and chnicopathological characteristics such as histological grade, clinicopathological stage of the rectal cancer. Assessing the significance of MMP2 and TIMP2 expression in rec-tal cancer for prognosis and treatment. Methods To test the expression level of MMP2 and TIMP2 in rectal caneer patients with immunohistochemisty method. Results were analysised with χ2 test. The Kaplan-Meier (Log-rank test) was used for univariate survival analysis. Results The positive rates of MMP2 and T1MP2 ex-pression in rectal cance are higher in comparison with normal tissues. With MMP2 have a trendence of increas-ing the positive expression of TIMP2 decreases. Conclusion MMP2 and TIMP2 relate obviously with the clini-copathological character of the rectal cancer. They may play an important role in the proliferation, invasion and of the cancer. Testing the level of expression of MMP2 and TIMP2 may be helpful to prejudge the prognosis of the patients with rectal cancer. Some new therapic methods relating to MMP2 and TIMP2 may give patients with rectal cancer a more satisfying treatment.
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Objective To investigate the expression of COX-2, VEGF, MMP-2 and P-g]ycoprotein in carcinoma of stomach and its significance. Method The expressions of COX-2, VEGF and P-glycoprotein inside and beside the tumor tissues of 57 cases carcinoma of stomach were detected with immunohistochemistry method. Result The expressions of COX-2, VEGF, MMP-2 and P-glyeoprotein inside the tumor tissues were significantly higher than that beside the tumor(χ2 = 5.29,5.37,5.62,4.87 ; P < 0.05). The expressions of COX-2, VEGF and MMP-2 were different among different carcinoma metastasis (χ2 = 5.97, 6.17,6.09 ; P < 0.05). P-glucoprotein expressions were positive correlated with gastric cancer(rs' = 0.674,0.65,0.67 ; P < 0.05). Conclusion COX-2, VGEF, MMP-2 and P-glyeopretein were some correlated and overexpressed in stomach carcinoma, which may take part in the genesis, development and multi-drug resistance of this cancer.
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Objective To investigate the localization coexpression in situ of matrix metalloproteinase(MMP)-2,-8 and vascular endothelial growth factor(VEGF)in human atherosclerotic unstable plaques with monocytes,smooth muscle cells(SMCs)and endothelial cells(ECs).Methods The histopathologic changes of unstable human atherosclerotic plaques were observed by hematoxylin and eosin(HE)staining,and the localization coexpression of MMP-2,MMP-8 and VEGF in the unstable human atherosclerotic plaques were observed by double fluorescent immunochemistry technology and confocal microscopy.Results The human atherosclerotic plaques in 6 cases had typical histopathologic instability,which was classified as super-Ⅳ type unstable plaques.The MMP-2 coexpression was the most obvious in the smooth muscle cells of fibrous cap infiltrated by monocyts,and in the monocytes of shoulder of plaques,and more expression of MMP-2 in the microvascular endothelial cells at the edge of shoulder and lipid necrosis;MMP-8 coexpressed obviously with the monocytes in the fibrous cap and lipid cores of plaques,and next to coexpressing in the smooth muscle cells of fibrous cap,while coexpression in endothelial cells was very little;VEGF coexpression was significant in the proliferative microvascular endothelial cells of plaques;The fibrous cap,which consisted of the smooth muscle cells mainly,and the edge of lipid necrosis infiltrated by more monocyts,were over-expression areas of VEGF.Conclnsions MMP-2,-8 and VEGF can coexpress with monocytes,SMCs and ECs in unstable plaques,and the major expression areas are in the fibrous cap,shoulder and micro-vessel at the edge of lipid necrosis,which are infiltrated by monocytes.Moreover,the outer membrane of vessel is involved in the pathogenesis of atherosclerosis.
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Objective To investigate the expression of VEGF-D and MMP-2 and explore their relationship with tumor invasion and local metastasis in pancreatic carcinoma.Methods The expression of VEGF-D and MMP-2 in 30 patients with pancreatic carcinomas and 6 cases with normal pancreatic tissues were detected by SABC immunohistochemical method.Results The positive rates of VEGF-D and MMP-2 proteins were 60%(18/30)and 66.7%(20/30)respectively,no expression of VEGF-D and MMP-2 was detected in normal pancreatie tissues.The expression of VEGF-D was significantly correlated with lymph node metastasis(P＜0.05),and the expression of MMP-2 was significantly correlated with lymph node metastasis and tumor local invasion(P＜0.05).The expression of VEGF-D protein Was positively correlated with MMP-2 protein(rs=0.54,P＜0.01).Conclusions There is a significantly positive correlation between high expression of VEGF-D and MMP-2 proteins in pancreatic carcinoma,and they may contribute to the invasive properties of pancreatic cancer.
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Objective To investigate the serum levels of CD147 and MMP-2 and the relationship between these proteins and colorectal tumor differentiation, Dukes stage. Methods Serum levels of CD147 and MMP-2 in 44 patients with colorectal carcinoma,28 polyp intestinal patients and 36 normal subjects were measured by ELISA. Results Serum levels of CD147(103.59±40.74pg/ml)and MMP-2(14.92±2.02ng/ml)in the cancer patients were significantly higher than those of the polyp intestinal(66.27±16.91;10:96±1.71)and normal control(63.84±18.71;10.49±1.61)(P＜0.05).The levels were associated with tumor differentiation and Dukes stage. Patients with poor differentiation had significantly higher levels of MMP-2 than those of patients with well differentiation. And Dukes C and D stage tumors had significantly higher levels of CD147 than Dukes A and B stage tumors(P＜0.05).The levels of CD147 and MMP-2 declined remarkably after one month of radical operation. Conversely, it decreased illegibly after palliative operation. The serum levels of CD147were positively correlated with MMP-2 in patients with colorectal cancer. Conclusion Elevated CD147 and MMP-2 serum levels are associated with tumor differentiation, invasion, metastasis. Dynamic alterations of serum CD147 and MMP-2 may be used as the indicators of diagnosis, the choice of operative method and the judgment of prognosis in patients with colorectal cancer.
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Objective To investigate edaravane in prevention of restenosis in rat common catery arteries balloon angioplasty and the possible mechanism of this process. Methods Forty male SD rats were randomly divided into 2 groups: treatment group (whose intima was injured by balloon and was given edaravone 3 mg/kg by peritoneal injection, bid) and control group (whose intima was injured by ballon and was given the same volume NS as edaravone). 1, 3, 7, 14 and 28 days after angioplasty, rats were killed and the local arteries were sectioned for analysis of pathological morphology and the expression of matrix metalloproteinase-2 (MMP-2) analyzed by immunohistochemistry. Results Small amounts of smooth muscle cell appeared at the intima of blood vessel 3 days after the artery injured by balloon. Consecutive intima was formed 7 days after artery injury. The intima was even or uneven thickened and the lumen of artery was significant stenosed 14 and 28 days afterwards. In the control group, the intimal area reached (0.240±0.043) mm2, the intima hyperplasy index were 0.52±0.06, stenosis ratio were 30%±9% 14 days afterwards. The intimal area were (0.420±0.063 )mm2, the intima hyperplasy index were 0.67± 0.07, stenosis ratio were 54%±9% on day 28. In the treatment group, the intimal area were (0.063± 0.025)mm2, the intima hyperplasy index were 0.24±0.07, stenosis ratio were 8%±3% after 14 days. The intimal area were (0.116±0.023) mm2, the intima hyperplasy index were 0.38±0.05, stenosis ratio were 16%±4% after 28 days. Compared with control group at the same time, the intimal area (F values were 50.488 and 81.119 respectively, P < 0.05 ), the intima hyperplasy index ( F values were 41.743 and 48.122 respectively, P<0.05) and stenosis ratio (F values were 24.221 and 81.119 respectively, P< 0.05) were decreased in treatment group. The expressions of MMP-2 raised after balloon injury. In control group, the expressions of MMP-2 were 27.16%±7.15% after 3 days, 22.59%±6.68% after 7 days, 18.85%±4.91% after 14 days. In the treatment group, it decreased to 15.57%±3.62% after 3 days, 12.91%±1.88% after 7 days. Compared with control group, the expressions of MMP-2 in treatment group were lower after 3 days and 7 days ( F = 8.359, P = 0.028 and F = 7.781, P = 0.032 ). Conclusions Edaravone can prevent restenosis in rat common catery after balloon angioplasty. The possible mechanism is that edaravone can inhibit the expressions of MMP-2 in this process.
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AIM: To study the effect of berberine(Ber) on invasion and migration of PG cells from a high metastatic human giant lung carcinoma cell line and to explore its mechanism. METHODS: Agarose drop method was used to detect PG migration; transwell cabin with FN in lower chamber was adopted to detect PG chemotaxis. PG adhesion to FN and martrigel was detected by MTT; PG invasive ability was determined by transwell cabin covered with martrigel. Expression of MMP2/TIMP2 protein and mRNA were detected by quantitative immunocytochemical method and RT - PCR respectively. RESULTS: After PG was treated by Ber( 10 mg/L) for 24 h: 1 ) migration distance of Ber- treated PG cells was markedly shorter than that of control cells (P ＜0. 01 ) and the number of passed membrane cells towards FN was much fewer than that of control cells ( P ＜ 0. 01 ); 2) PG adhesion to FN and martrigel was inhibited remarkably by Ber compared with control PG; 3) the migration of PG cells through the martrigel -coated transwell was significantly inhibited by the addition of Ber; 4) MMP2 expression was reduced significantly(P ＜0. 01 ), while the TIMP2 expression showed up - regulating tendency, but had no differences compared with control group (P ＞ 0. 05). The MMP2/TIMP2 ratio was decreased; 5 )the MMP2 mRNA/TIMP2 mRNA ratio was decreased by Ber. CONCLUSION: Inhibition of cell migration, adhesion to ECM and invasion into ECM of tumor cells and regulation of homeostasis between MMPs and TIMPs to maintain ECM integrity may be the basic mechanism of inhibitive effect of Ber on invasion and metastasis of tumors.
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Objective To study the expressions of RhoC and MMP-2 proteins in epithelial ovarian cancer and their clinical significances in order to provid the basis for assessing the biological behaviour of epithelial ovarian cancer.Methods Immunohistochemistry was used to detect the expressions of RhoC and MMP-2 proteins in 10 cases of normal ovarian tissues,12 cases of epithelial benign ovarian tumor and 91 cases of epithelial ovarian cancer,and the relationship with the clinical features was analyzed.Results The RhoC and MMP-2 proteins positive expression rates in ovarian benign tumor and ovarian normal tissues were 0 respectively; the positive expression rates of RhoC and MMP-2 proteins in epithelial ovarian cancer were 37.3% and 68.1%.The expressions of RhoC and MMP-2 proteins in ovarian cancer were significantly higher than those in ovarian benign tumor and ovarian normal tissues.The positive expression rates of RhoC and MMP-2 in moderately and poorly differentiated cancer were significantly higher than those in well differentiated cancer(P
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OBJECTIVE To understand the function of MMP-2 and TIMP-2 and the relationship among expression of MMP-2, TIMP-2 and microvessel density in laryngeal carcinomas. METHODS The expression of MMP-2, TIMP-2 and CD34 in 37 laryngeal carcinomas patients were studied with immunohistochemical staining. The staining results were studied morphometrically with computer image analysis. RESULTS The mean values of MMP-2 expression and microvessel density (MVD) in squamous cell carcinoma group with lymph node metastasis were significantly higher than that without lymph node metastasis (P
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Objective To study the change of matrix metalloproteinase-2 (MMP-2) in the development of renal fibrosis and evaluate the diagnostic value of blood MMP-2 level in renal fibrosis.Methods Thirty three patients with chronic glomerulonephritis were divided into proliferation group(n=18) and fibrosis group(n=15) according to renal fibrosis degree in renal pathology.Another 8 healthy subjects were used as control group.The levels of pro-MMP-2 and MMP-2 in serum were measured with the method of SDS-PAGE enzymography.Then the levels of pro-MMP-2 and MMP-2 in serum were compared between various groups.Results The serum MMP-2 level in proliferation group was much higher than that in control group(P0.05).Conclusion There is a significant difference of serum MMP-2 between suffering group and normal control group.Therefore the detection of serum MMP-2 level can be conducive to understand the development of disease and estimate prognosis.
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Objective To study the inhibitory effects of Probucol on the expressions of serum promatrix metalloproteinase-2(pro-MMP-2) and matrix metalloproteinase-2(MMP-2) in patients with coronary heart disease(CHD).Methods The levels of serum Pro-MMP-2 and MMP-2 were detected by zymograph and total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)were measured by enzyme method in 30 CHD patients before and after treatment with Probucol.Results After treatment of Probucol,the expression levels of pro-MMP-2,MMP-2,TC and LDL-C in serum were decreased than those before treatment,respectively;there were obvious differences of various indexes mentioned above between before and after treatment(P0.05).Conclusion Probucol can inhibit the expressions of pro-MMP-2 and MMP-2 in serum as same as TC and LDL-C.Probucol,as one of TIMPs,may be applied to stabilize plaque..
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Objective To investigate the invasion ability and collagenolytic activity of human glioma cells in vitro.Methods Boyden chamber invasion assay was employed to evaluate the cell migration ability of human malignant glioma cell line U87MG in vitro and the effect of conditioned medium of U87MG cells on matrix collagenolytic activity was tested by agar-gelatin gel.Results The number of U87MG glioma cells migrating through the Matrigel-coated membrane was more than that of addition of EDTA or anti-MMP-2 antibody in U87MG glioma cells(P0.05).EDTA or anti-MMP-2 antibody markedly inhibited the number of the migrated cells,the inhibitory rates were 79.2% and 77.1%,respectively. The conditioned medium collected from the U87MG cells showed an increase in the transparent ring area on agar-gelatin gel.Inhibition of MMP-2 enzymatic activity by EDTA or anti-MMP-2 antibody reduced the transparent ring area on agar-gelatin gel.Conclusion Both invasion ability and collagenolytic activity of U87MG cells are depended on MMP-2,suggesting that MMP-2 plays an important role in glioma invasiveness.
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0.05).However the MMP-2 and pro MMP-2 concentrations were still higher 30 d after implantation(13 935?2 167,15 628?1 739 INT?mm~2 vs 11 568?2 219,13 649?1 894 INT?mm~2,P
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Objective To study the expressions of matrix metalloproteinases-2 (MMP-2) and its tissue inhibitor-2 (TIMP-2) and microvessel density (MVD) in human endometrial carcinoma tissues and their relations with the invasion and metastasis of endometrial carcinoma. Methods Immunohistochemistry was used to measure the MMP-2, TIMP-2, and MVD protein levels in 33 patients with endometrial carcinoma and 8 normal endometrial samples. Results The MMP-2, TIMP-2 and MVD protein expressed in both normal endometrial samples and endometrial carcinoma. The positive expression proportions of MMP-2, TIMP-2, and MVD protein in endometrial carcinoma tissues were higher than those in normal endometrial samples (P
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Objective To investigate the correlations of serum matrix metalloproteinase-2, -9 (MMP-2, MMP-9) contents and tissue expressions in hepatocellular carcinoma with tumor invasion and metastasis. Methods Serum MMP-2, MMP-9 contents were detected in 40 patient with hepatocellular carcinoma and 20 healthy controls by ELISA; the expressions and distributions of MMP-2 and MMP-9 in 40 patients and 10 normal tissues were detected by immunohistochemical method. Results Serum MMP-2, MMP-9 contents were significantly elevated in cancer samples compared with normal serum (P
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Objective: To investigate the expressions of MMP-2 and MMP-7 between colorectal cancer and normal tissue.Methods: RT-PCR was used to determine the expressions of MMP-2 and MMP-7 in colorectal cancer and normal tissue.Results: The expression rate and level of MMP-2 and MMP-7 were higher in cancerous tissue than that in normal tissue(P
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IL-1beta is known promote cyclooxygenase-2 (COX- 2) and matrix metalloproteinase-2 (MMP-2) expression. This study focuses on the characterization of the signaling cascade associated with IL-1beta-induced matrix metalloproteinase-2 (MMP- 2) regulation in human chondrocytes. The decrease in collagen levels in the conditioned media was prevented by a broad spectrum MMP inhibitor, suggesting that IL-1beta promotes the proteolytic process leading to MMP-2 activation. IL-1beta-related MMP-2 expression was found to be dependent on prostaglandin E2 (PGE2) production. In addition, the induction of COX-2 and MMP-2 was inhibited by the pretreatment of chondrocytes with a SB203580 or Ro 31-8220, indicating the involvement of protein kinase C (PKC) or p38 mitogen-activated protein kinase (MAPK). However, there is no cross-talk between PKC and p38 MAPK in the IL-1beta-induced MMP-2 activation. Taken together, these results demonstrated that IL-1beta induces MMP-2 expression through the PGE2-dependent mechanism in human chondrocytes.
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Humans , Chondrocytes/drug effects , Dinoprostone/analysis , Matrix Metalloproteinase 2/analysis , Indoles/pharmacology , Interleukin-1/pharmacology , Isoenzymes/antagonists & inhibitors , Nitrobenzenes/pharmacology , Phosphorylation/drug effects , Prostaglandin-Endoperoxide Synthases/metabolism , Protein Kinase C/antagonists & inhibitors , Sulfonamides/pharmacology , Up-Regulation , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
BACKGROUND: The activation of proMMP-2 is induced by membrane type 1-matrix metalloproteinase (MT1-MMP), but inhibited by tissue inhibitors of matrix metalloproteinase type 2 (TIMP-2). This study was carried out to establish the pattern of mRNA expression of MMP-2, MT1-MMP, and TIMP-2 in breast carcinomas. METHODS: Seventy-nine cases of invasive ductal carcinoma, 10 of ductal carcinoma in situ, and 10 of fibrocystic disease as a control were analysed for the expression of MMP-2, MT1-MMP, and TIMP-2 mRNA, using in situ hybridization. Correlations of the results with the clinical stage, tumor size, nodal status, and nuclear grade were analysed. RESULTS: The expression rates of MMP-2, MT1-MMP, and TIMP-2 mRNA in invasive ductal carcinoma were 68%, 73%, and 56%, respectively. They were localized to both stromal and tumor cells, but mainly in the latter. The MMP-2 mRNA expression was significantly correlated with the clinical stage (p < 0.05), while the expression of TIMP-2 mRNA was inversely correlated with clinical stage and tumor size(p < 0.05). Significant positive correlations between MMP-2 and MT1-MMP expressions, along with inverse relationships between MMP-2 and TIMP-2, and between TIMP-2 and MT1-MMP, were also found. CONCLUSIONS: MMP-2 and TIMP-2 mRNA expressions might be useful as one of a range of prognostic parameters in breast carcinoma patients.