Correlation of c-MET and CXCR4 proteins and microvessel density with liver metastasis in colorectal cancer / 肿瘤研究与临床

Objective:To explore the correlation of c-MET and CXCR4 proteins and microvessel density (MVD) with liver metastasis in colorectal cancer tissues.Methods:A total of 40 colorectal cancer tissue samples and 10 paracancerous (5 cm from the edge of the tumor) normal colorectal tissue samples were collected from March 2015 to December 2020 in Shanxi Traditional Chinese Medical Hospital. Among 40 patients with colorectal cancer, 15 patients had liver metastasis. Immunohistochemistry was used to detect c-MET protein, CXCR4 protein and CD34-labeled MVD in various tissues, and the relationships between them and liver metastasis and between the three were analyzed.Results:The positive rates of c-MET protein [72.5% (29/40) vs. 30.0% (3/10)], CXCR4 protein [47.5% (19/40) vs. 10.0% (1/10)] and MVD (20.1±5.2 vs. 11.5±4.3) in colorectal cancer tissues were higher than those in paracancerous tissues, and the differences were statistically significant (all P < 0.05). The positive rates of c-MET protein [86.7% (13/15) vs. 64.0% (16/25)] and CXCR4 protein [66.7% (10/15) vs. 36.0% (9/25)] in colorectal cancer liver metastasis group were significantly higher than those in non-liver metastasis group, and the differences were statistically significant (both P < 0.05). MVD in colorectal cancer liver metastasis group was significantly higher than that in non-liver metastasis group (21.5±5.3 vs. 12.4±5.7), and the difference was statistically significant ( P < 0.05). In colorectal cancer tissues, c-MET protein expression was positively correlated with CXCR4 protein expression ( r = 0.568, P < 0.05), and MVD in c-MET-positive patients or CXCR4-positive patients was higher than that in negative ones (both P < 0.05). Conclusions:The c-MET protein, CXCR4 protein and MVD may play important roles in the liver metastasis of colorectal cancer. The three indicators can provide a certain reference for the early diagnosis and prognosis prediction of liver metastasis of colorectal cancer.

Expression of c-Met and c-Src in non-small cell lung cancer and its relationship with prognosis / 中国医师进修杂志

Objective To explore the expressions of c-Met and c-Src in non-small cell lung cancer (NSCLC), and its relationship with clinical pathological characters and prognosis. Methods The c-Met and c-Src expressions were detected by immunohistochemistry in 88 patients with NSCLC from April 2011 to January 2013. The relationship between the expressions of c-Met and c-Src and clinical pathological features and prognosis were analyzed. Results The c-Met and c-Src were all significantly expressed in NSCLC tissues, and no expression showed in interstitial and normal lung tissues. The expressions of c-Met and c-Src in patients with NSCLC were associated with sex, differentiation, pathology type, T staging and TNM staging (P<0.05 or <0.01); and the expression of c-Met was associated with lymph node metastasis (P<0.01). The expressions of c-Met and c-Src in patients with NSCLC were not associated with age, and the expression of c-Src was not associated with lymph node metastasis (P>0.05). Pearson correlation analysis result showed that the expressions of c-Met and c-Src in lung cancer tissues was positive correlation (r=0.662, P<0.01). Kaplan-Meier survival curve analysis result showed that the disease free survival time (DFS) and overall survival time (OS) in c-Met high expression patients (51 cases) were significantly shorter than those in c-Met low expression patients (37 cases): (18.08 ± 1.34) months vs. (23.76 ± 1.79) months and (33.63 ± 1.95) months vs. (42.24 ± 2.68) months, the DFS and OS in c-Src high expression patients (25 cases) were significantly shorter than those in c-Src low expression patients (63 cases): (16.96 ± 2.56) months vs. (21.86 ± 1.15) months and (27.84 ± 2.89) months vs. (40.98 ± 1.81) months, the DFS and OS in both c-Met and c-Src high expression patients (25 cases) were significantly shorter than those in both c-Met and c-Src low expression patients (37 cases): (16.96 ± 2.56) months vs. (23.76 ± 1.79) months and (27.84 ± 2.89) months vs. (42.24 ± 2.68) months, and there were statistical differences (P<0.05). Cox multiplicity result showed that T staging (RR=2.174, 95％CI 1.354 to 3.490, P=0.001) and high expressions of c-Met and c-Src (RR=1.447, 95％CI 1.114 to 1.880, P=0.006) were the independent risk factors of DFS in patients with NSCLC;pathology type (RR=0.610, 95％CI 0.377 to 0.986, P=0.044), T staging (RR=2.215, 95％CI 1.357 to 3.616, P=0.001) and high expressions of c-Met and c-Src (RR=1.979, 95％CI 1.455 to 2.692, P = 0.000) were the independent risk factors of OS in patients with NSCLC. Conclusions The c-Met and c-Src are involved in the development of NSCLC and affect the prognosis of patients with NSCLC.

Correlation between expression of C-met and epidermal growth factor receptor-tyrosine kinase inhibitor resistance in lung adenocarcinoma / 肿瘤研究与临床

Objective To detect C-met protein expression and gene amplification in lung adenocarcinoma, and to analyze their relationship with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance and prognosis. Methods A total of 120 cases of lung adenocarcinoma diagnosed in Shanxi Provincial Cancer Hospital from January 2011 to May 2013 were selected. The expressions of C-met protein and C-met gene amplification were conducted by immunohistochemistry (IHC) method and fluorescence in situ hybridization (FISH), and all patients were followed up. The relationship between the expression of C-met protein and gene amplification with clinicopathological features and EGFR-TKI resistance and prognosis were analyzed. Results The high expression of C-met protein and gene amplification in 120 tissues were 17.5 ％ (21/120), 10.83 ％ (13/120). Of the 80 patients treated with EGFR-TKI, the incidence of C-met protein high expression was 30.43 ％ (14/46) in patients with drug resistance, which was significantly higher than that in patients without drug resistance (11.76 ％, 4/34), the difference was statistically significant (χ2= 3.908, P= 0.048). The rate of C-met gene amplification was 19.57 ％ (9/46) in patients with drug resistance,which was significantly higher than that in patients without drug resistance (2.94 ％, 1/34) the difference was statistically significant (P= 0.038). The expression of C-met protein in 46 patients with drug resistance was positively correlated with gene amplification (r= 0.388, P= 0.008), but in 40 patients without TKI, the expression of C-met protein was not correlated with gene amplification (r=0.279, P=0.081). The high expression of C-met protein was correlated with age, pathological grade and clinical stage (all P<0.05), while C-met gene amplification was related to clinical stage (P=0.036). Cox regression analysis suggested that C-met gene amplification was an independent prognostic factor (P= 0.034). Conclusions C-met protein expression and gene amplification are risk factors for EGFR-TKI resistance. C-met gene amplification suggests poor prognosis, and can be used as an independent factor for prognostic evaluation.

Expression of the c-MET, HGF and VEGF biomarkers in intestinal and diffuse gastric cancer in the Brazilian population: a pilot study for the standardization of the quantitative PCR technique

Background: Gastric carcinoma (GC) is the third leading cause of death among malignant tumors worldwide, causing approximately 900,000 deaths/year. Changes in oncogenes that encode tyrosine kinase receptors play an important role in the pathogenesis of GC. MET gene is a proto-oncogene that encodes a tyrosine kinase receptor c-MET and it is required for embryonic development and tissue repair. The hepatocyte growth factor (HGF) is the only known ligand for c-Met receptor. The MET oncogene activation suppresses apoptosis and promotes the survival, proliferation, migration, differentiation and angiogenesis of cells. Among the angiogenic factors, VEGF is the main regulator. Its biological function includes the promotion of endothelial cells mitosis to stimulate cells proliferation. These biomarkers expression in GC is relatively recent and population-based studies are required to define the expression pattern. The aim of this study was to determine qPCR technical standardization to evaluate quantitatively, in paraffin tissue samples, the presence of gene 23 expression of the MET, HGF and VEGF in diffuse and intestinal GC types. Methods: Twenty GC patients were studied, 10 patients were intestinal-type GC (average age 72.1 years) and 10 diffuse-type (average age 50.1 years). In all patients, tissue samples were analyzed from the tumor and distant areas of the tumor tissue. The relative expressions of the tumor markers c-Met, HGF and VEGF were performed by qPCR technique by comparing tumor and non-tumoral samples and they were normalized with the GAPDH constitutive gene. Statistical analysis was performed through T-test. Results: For c-Met, 18/20 (90%) patients expressed the marker and 9/20 (45%) overexpressed this gene, in which three were intestinal-type GC and six were diffuse-type GC. For HGF, only 7/20 (35%) patients expressed this gene and it was overexpressed in 4/20 (20%), in which two were intestinal-type GC and two were diffuse-type GC. For VEGF, 20/20 (100%) patients expressed this marker and in 12/20 (60%) were observed overexpression, in which eight patients had diffuse-type GC and four had intestinal-type GC. Conclusions: qPCR technique was standardized and suitable for expression analysis of the three biomarkers using paraffin embedded tissue samples. Further studies should be carried out to characterize the expression pattern of these biomarkers in GC in the Brazilian population (AU)

Expression of bcl-2 and c-Met genes in non-small cell lung cancer cell lines harboring different mutations of epidermal growth factor receptor / 肿瘤研究与临床

Objective To detect the expression of bcl-2 and c-Met genes in lung cancer cell lines with different mutations of epidermal growth factor receptor (EGFR), in order to explore the association between expression of bcl-2 and c-Met genes and drug resistance in non-small cell lung cancer (NSCLC). Methods Direct sequencing was used to detect EGFR mutations status in HCC827 cells, A549 cells and H1975 cells. Immunocytochemistry was conducted to test bcl-2 and c-Met expression. RT-PCR was performed to analyzed bcl-2 gene expression and ARMS was used to detect EGFR mutations status in malignant pleural effusion of NSCLC patients. Results A549 cells, HCC827 cells and H1975 cells were EGFR wild type, EGFR exon 19 deletion (19del), and EGFR exon 21 L858R and exon 20 T790M double mutations. c-Met and bcl-2 protein located in cytoplasm and the intensity of positive expression was highest in HCC827 cells, followed by A549 cells and H1975 cells. The bcl-2 mRNA expression was higher in HCC827 and A549 cells than that in H1975 cells (10.93±1.90 vs. 0.83±0.15, P=0.013; 7.13±1.33 vs. 0.83±0.15, P= 0.000). However bcl-2 mRNA expression was not associated with EGFR mutations (wild type, 19del and L858R) in malignant pleural effusion of NSCLC patients. Conclusion bcl-2 and c-Met gene in HCC827 cells (EGFR 19del) expression is significantly higher than those in H1975 cells (EGFR L858R/T790M), implying EGFR L858R mutations and 19del mutations may be regulated by different signaling pathways.

Research progress of HGF/c-MET signaling pathway inhibitors in anti-pancreatic cancer / 国际肿瘤学杂志

Pancreatic cancer is one of the most malignant tumors.Targeted therapy has become an important part of the treatment of pancreatic cancer.The signaling pathways such as hepatocyte growth factor/c-MET (HGF/c-MET) signaling pathway, inhibition of which may exerts an antitumor effect, play extremely important roles in the occurrence and development of pancreatic cancer.Therefore, the research of HGF/c-MET targeted inhibitors opens up a new avenue for treatment of pancreatic cancer.

Role of Recepteur D'origine Nantais on Gastric Cancer Development and Progression / 전남의대학술지

Recepteur d'origine nantais (RON) is a receptor tyrosine kinase belonging to the subfamily of which c-MET is the prototype. Large epidemiologic studies have confirmed the strong association between RON and gastric cancer development. Constitutive activation of RON signaling directly correlates with tumorigenic phenotypes of gastric cancer and a poor survival rate in advanced gastric cancer patients. In this review, we focus on recent evidence of the aberrant expression and activation of RON in gastric cancer tumors and provide insights into the mechanism of RON signaling associated with gastric cancer progression and metastasis. Current therapeutics against RON in gastric cancer are summarized.

Role of Recepteur D'origine Nantais on Gastric Cancer Development and Progression / 전남의대학술지

Recepteur d'origine nantais (RON) is a receptor tyrosine kinase belonging to the subfamily of which c-MET is the prototype. Large epidemiologic studies have confirmed the strong association between RON and gastric cancer development. Constitutive activation of RON signaling directly correlates with tumorigenic phenotypes of gastric cancer and a poor survival rate in advanced gastric cancer patients. In this review, we focus on recent evidence of the aberrant expression and activation of RON in gastric cancer tumors and provide insights into the mechanism of RON signaling associated with gastric cancer progression and metastasis. Current therapeutics against RON in gastric cancer are summarized.

Pharmacodynamic screening of anticancer agents used as c-Met inhibitor in vitro and in vivo / 天津医药

Objective To screen 8 series of LY compounds, c-Met tyrosine kinase inhibitors, and evaluate their anti-tumor effects in vitro and in vivo. Methods Preliminary screening was carried out by detecting the c-Met kinase phosphor?ylation inhibition activity of the compounds. CCK-8 assay was adopted for secondary anti-tumor screen of the selected com?pounds using MKN-45, U87MG, Caki-1 and PC-3 cell lines in vitro. The transplanted tumor model of U87MG cells in nude mice was established to evaluate the antitumor activity in vivo. Results Four compounds (LY22, LY25, LY28 and LY32) with better activities were selected by HTRF method, in which LY28 had better inhibitory effect on c-Met than that of Crizo?tinib. The above active compounds showed different degrees of inhibition on the four kinds of target cells (MKN-45, U87MG, Caki-1 and PC-3) detected by CCK-8 method, and the inhibitory effect of LY28 showed the most obvious. Antitumor activi?ty in vivo showed that LY28 can significantly inhibited tumor growth in a dose-dependent manner. The tumor inhibitory rate in high-dose of LY28 was 78.13%. Conclusion The compound LY28 has good antitumor activity in vitro and in vivo, which will be a new tyrosine kinase inhibitor.

Metastasis-associated in colon cancer 1 and its role in cancer / 国际肿瘤学杂志

The protein product of metastasis-associated in colon cancer 1 (MACC1) gene induces the activation of hepatocyte growth factor/mesenchymal-epithelial transition factor (HGF/c-Met) signaling pathway through transcriptionally activating c-Met gene and upregulating its expression to further promote tumor invasion and metastasis.High level expression of MACC1 is associated with the occurrence and metastasis of a wide variety of human tumors, such as colon cancer, gastric cancer, liver cancer, lung cancer, ovarian cancer etc.In addition, the overexpression of MACC1 is also closely associated with clinical TNM stages and distant metastasis.Thus, MACC1 can serve as an independent indicator of tumor metastasis and prognosis, and become a new target for gene therapy.

Research progress in c-Met and hepatocellular carcinoma / 临床肝胆病杂志

c-Met plays a pivotal role in the development and progression of hepatocellular carcinoma (HCC), which can lead to proliferation, survival, cytoskeleton reorganization, separation and diffusion, and angiogenesis of tumor cells. Moreover, c-Met is an important prognostic factor for HCC. In HCC, c-Met acts as an activator of a series of signaling pathways, including PI3K/AKT/mTOR, ERK/MAPK, and Rac-Pak. In recent years, it has been reported that small-molecule kinase inhibitors can abolish phosphorylation at the intracellular carboxyl terminal of c-Met, and then inhibit the recruitment of signal convertors and downstream signaling pathways, which finally achieve anti-tumor activities. Based on the carcinogenic activity of c-Met in HCC, this paper points out that selective inhibitors of c-Met hold promise for targeted therapies for HCC.

Expressions of MACC1 and c-Met genes in prostate cancer tissues / 天津医药

Objective This study is to investigate the expressions of MACC1 and c-Met genes in prostate cancer tis?sues and to explore the relationship between these gene expressions with the development, invasion and metastasis of pros?tate cancer. Methods The expressions of MACC1 and c-Met genes were examined in 30 cases of benign prostatic hyperpla?sia and 67 cases of prostate cancer using citron acid-microwave-SP immunohistochemical method and analysed with their clinical pathological features. Results Expressions of MACC1 and c-Met in prostate tissues show statistical difference ac?cording to Gleason score, PSA level, pathological stages and whether bone metastasis occurs after radical surgery ( P<0.05 or P < 0.01), but their expressions in prostate tissue show no significant difference among different sex, age and whether smoking or not. Expression of MACC1 in prostate tissue of stageⅢandⅣcancer is significantly higher than that in benign prostatic hyperplasia (BPH) tissues (P<0.05) while the expression of c-Met only shows statistical difference in prostate tis?sue of stage Ⅳcancer compared with that in BPH (P < 0.05). There is a positive correlation between the expression of MACC1 with expression of c-Met in prostate cancer tissues (P<0.01). Kaplan-Meier curves revealed that the survival rates was lower and survival time of bone-free metastasis were shorter in patients with high MACC1 and c-Met expressions in prostate tissue than those with low expressions of MACC1 and c-Met in prostate tissue. Conclusion Expression of MACC1 and c-Met is closely related to the development, invasion and metastasis of prostate cancer, so MACC 1 and c-Met may be used as promising diagnostic and prognostic markers for prostate tumor, and as new therapeutic targets for prostate cancer.

Expression of c-MET in Invasive Meningioma

BACKGROUND: Meningiomas show high recurrence rates even after curative tumor removal. The invasiveness of meningiomas may contribute to their high recurrence rates. Recently, c-MET and hepatocyte growth factor (HGF) have been reported to be involved in cancer invasion. METHODS: We examined the immunohistochemical expression of c-MET and HGF in 100 cases of patients with meningiomas who have undergone complete tumor removal. RESULTS: c-MET(-High) and HGF(-High) were found in 17% and 13% of meningiomas, respectively. Brain invasion was observed in 17.6% of c-MET(-High) meningiomas, but in only 2.4% of c-MET(-Low) meningiomas (p=.033). Bone/soft tissue invasion was observed in 23.5% of c-MET(-High) meningiomas and in 9.6% of c-MET(-Low) meningiomas (p=.119). HGF(-High) did not show statistical association with brain invasion or bone/soft tissue invasion. c-MET(-High) demonstrated shorter recurrence-free survival (RFS, 93.5+/-8.2 months vs 96.1+/-1.9 months); however, this difference was not statistically significant (p=.139). There was no association of HGF(-High) with RFS. CONCLUSIONS: This study demonstrates that c-MET(-High) is associated with brain invasion of meningiomas, and that c-MET expression may be a useful predictive marker for meningioma recurrence. Patients with invasive meningiomas with high expressions of c-MET may be good candidates for targeted therapy using c-MET inhibitors.

Abnormal activation of c-Met in lung cancer and research progress of the targeted drugs: A review / 第二军医大学学报

c-Met is a receptor tyrosine kinase (RTK) with hepatocyte growth factor (HGF) as its natural ligand. c-Met may be activated in a ligand-dependent manner by binding HGF or in a ligand-independent manner. Diverse activation mechanisms of c-Met exist in many malignant tumors, including lung cancer. Moreover, the abnormal activation of c-Met has a close relationship with the occurrence, development and malignant biological behavior of lung cancer. This paper focused on the different activation mechanisms of c-Met in non-small cell lung cancer and small cell lung cancer and also reviewed the research progress of c-Met targeted drugs in lung cancer.

Expressions and significance of HGF,C-met and NRP1 protein in osteosarcoma / 重庆医学

Objective Todetect the expressions of HGF ,C-met and NRP1 protein in osteosarcoma and to investigate their corre-lation and the clinical significance .Methods The postoperative preserved paraffin block and the clinical data in 70 cases of osteosar-coma were taken as the observation group and 50 cases of the parraffin block of mature bone tissue after decalcification and the clin-ical data were taken as the control group .The expressions of HGF ,C-met and NRP1 protein were detected by the immunohisto-chemistry(IHC) method for investigating their expressions in the tumor patients with different clinicopathological characteristics and analyzing their relationship .Results The positive rates of HGF ,C-met and NRP1 expressions in the observation group were higher than those in the control group .The positive rates of HGF ,C-met and NRP1 expressions in the observation group were cor-related with metastasis ,vascular invasion ,clinical stage and Ki67 expression .The positive relationship was found between the ex-pressions of HGF and C-met with NRP1 of neoplasm .Conclusion The high expressions of HGF ,C-met and NRP1 in osteosarcoma play the important role in the progress of tumor lesion .The postoperative combined detection of HGF ,C-met and NRP1 protein could have certain value to predict the prognosis .

Expression of MACC1 and C-MET proteins in hepatocellular carcinoma and its clinical relevance / 中华普通外科杂志

Objective To explore the expression and clinical relevance of metastasis-associated colon cancer-1 (MACC1) and C-MET proteins in hepatocellular carcinoma (HCC) tissue.Methods The expressions of MACC1 and C-MET were detected in 51 specimens of HCC and paraneoplastic liver tissue,normal liver tissue in 13 healthy cases using immunohistochemistry and Western blotting.The correlations of the expressions of MACC1 and C-MET proteins were evaluated,survival rates were observed,the relationship between the expression of MACC1,C-MET proteins and the clinicopathologic features of HCC were analyzed.Results The positive rate of MACC1 and C-MET proteins was 80.4％ and 76.5％ in HCC tissue,the relative expressions were 0.645 ± 0.047 and 0.504 ± 0.023 respectively,which was significantly different from those in paraneoplastic liver tissue and normal liver tissue (respectively F =173.308,252.817,all P =0.000).The survival analysis showed that the three-year survival rate in patients with positive MACC1 and C-MET expressions was significantly lower than that in patients with negative expressions (respectively x2 =3.934,4.439,all P ＜ 0.05),the positive rate and relative expressions of MACC1 and C-MET were significantly correlated with TNM stage,portal vein cancer thrombus and pathology typing (P ＜ 0.05).Conclusions The expression of MACC1 and C-MET is associated with the malignant progression of HCC.MACC1 may serve as a independent prognostic factor for advanced HCC and a possible therapy target for the treatment of HCC.

XL-880 increases radiosensitivity of breast cancer cells / 中华普通外科杂志

Objective To evaluate the effects of Met inhibitor XL-880 on radiosensitivity of breast cancer cells MDA-MB-231.Methods MDA-MB-231 cell lines were assigned to the following treatment groups:control group,radiation group,XL-880 group and combination group.Cell apoptosis,cell cycle distributions and tumorigenicity were investigated by flow cytometry or clonogenic assay.The expression of apoptosis and cell cycle related proteins (p21,Cyclin B1,Bcl-2,Caspase-3 and PARP),and phosphorylation levels of c-Met were measured by Western blot.Results XL-880 combined with radiation significantly decreased the proliferation activity of MDA-MB-231 cells (P ＜ 0.05).Flow cytometry results showed that the rate of G2/M cell were increased with XL-880 (P ＜ 0.05),and the rate were (17.3 ±1.3) ％,(20.0 ± 4.0) ％,(28.5 ± 3.1) ％,(57.0 ± 3.3) ％,respectively.Annexin V/PI double-staining assay showed that XL-880 obviously induced the apoptosis of MDA-MB-231 cells after radiation (P ＜ 0.05),of which the apoptotic rates were (7.3 ±0.9)％,(14.1 ±0.6)％,(35.5 ±4.4)％,(48.2±5.3)％,respectively.XL-880 downregulated the expressions of Cyclin B1 and anti-apoptosis protein Bcl-2,while promoted the expression of apoptosis related protein cleaved Caspase-3 and PARP.Conclusions XL-880 enhance the radiosensitivity of breast cancer cell MDA-MB-231 by inhibiting Met pathway.

Expression and clinical significance of hepatocyte growth factor receptor and epidermal growth factor receptor in pancreatic cancer / 中华肝胆外科杂志

Objective To determine the clinical significance of hepatocyte growth factor receptor (Met) and epidermal growth factor receptor (EGFR) in the clinicopathology and prognosis of pancreatic cancer.Methods 70 patients admitted with pancreatic cancer from 1995 to 2005 were retrospectively analyzed with clinicopathological and follow-up data.Expression of Met and EGFR in cancer nest embedded with paraffin were detected by immunohislostaining (EnVision method) and correlation with clinicopathologic parameters and mutual correlation between these two receptors were further analyzed.Prognosis and related risk factors were analyzed by Kaplan-Meier survival analysis and Cox regression analysis,respectively.Results Both Met and EGFR significantly correlated with TNM staging,tumor size and superior mesenteric vessels invasion (P＜0.05).Expression level of Met positively correlated with that of EGFR (r9 =0.658,P＜0.05).Both Met and EGFR significantly correlated with patients' survival (P＜0.05) and Met was an independent prognostic risk factor for pancreatic cancer.Conclusions Both Met and EGFR significantly affect development and prognosis of pancreatic cancer and correlate with each other.Simultaneously targeting both Met and EGFR pathways may provide an advisable strategy of targeted therapy in pancreatic cancer.

Changes in expression of hepatocyte growth factor and c-met in lungs in a rat model of pulmonary hypertension / 中华麻醉学杂志

Objective To investgate the changes in the expression of hepatocyte growth factor (HGF)and c-met in the lungs in a rat model of pulmonary hypertension.Methods Eighty 7 week old male SD rats weighing 180-250 g were randomly divided into 2 groups ( n =40 each ):control group (group C) and pulmonary hypertension group (group PH).Pulmonary hypertension was induced by left pneumonectomy and subcutaneous monocrotaline (MCT) 60 mg/kg 2 weeks later.Pulmonary artery pressure and the ratio between the weight of right ventricle and left ventricle + interventricular septum ( RV/LV + S) were measured at 7,14,21 and 28 d after MCT administration.HGF and c-met protein and mRNA expression and TGF-β content in the lung tissue were determined.Results Pulmonary hypertension and right ventricular hypertrophy associated with hypertrophy of pulmonary artery tunica media and muscularization of small pulmonary arteries developed after MCT administration in PH group.In PH group HGF protein and mRNA expression in the lungs was significantly down-regulated as compared with group C.There were no significant differences in c-met protein and mRNA expression in the lungs between the 2 groups.The TGF-β content in the lungs was significantly increased in group PH as compared with group C.Conclusion Decrease in HGF production in the lungs plays an important role in the pulmonary hypertension.Increasing of pulmonary TGF-β may play an important role in the down-regulation of pulmonary HGF expression during pulmonary hypertension.

Effects of c-Met inhibitor SU11274 on basal-like breast cancer cells MDA-MB-231 / 中华普通外科杂志

Objective To investigate the effects of a new c-Met inhibitor SU11274 on apoptosis and motility of c-Met-positive basal-like breast cancer cells MDA-MB-231. Methods The concentrations of SUl1274 were set to 0,0.1,1,10 and 20 μmol/L.Morphological change of apoptotic cells was analyzed by Hoechst33342,MitroTrackerRed and Yo-pro-1 staining.The apoptotic rate of MDA-MB-231 cells were determined by Annexin V/PI double-staining. The expression of apoptosis related proteins (Bcl-XL,Caspase-3 and PARP) and phosphorylation levels of c-Met and Akt were analyzed by Western blot.The capability of motility were measured by wound-healing assay and chemotaxis assay. Results After treatment by SU11274( 10 μmol/L) for 48 h,shrinking apoptotic cells of MDA-MB-231 was observed by flurescent microscope and nuclear fragmentation was seen.Annexin V/PI double-staining showed SU11274induced apoptosis of MDA-MB-231 cells (P ＜ 0.05 ),and the apoptotic rates were (7.3 ± 0.9) ％,( 14.1 ±0.6) ％,(35.5 ± 4.4) ％ and (48.2 ± 5.3 ) ％,respectively.SU11274 downregulated the expression of Bcl-XL and promoted the dissection of Caspase-3 and PARP in a dose dependent relationship.SU11274 prolongs the wound-healing time,decreases the migration cell count (P ＜ 0.05 ) and effectively inhibits the phosphorylation of c-Met and its downstream key proteins Akt in a dose-dependent manner.Conclusions C-Met inhibitor SU11274 induces apoptosis and inhibits the motility of c-Met-positive basallike breast cancer cell line MDA-MB-231,probably through inhibiting phosphorylation of c-Met/PI3K/Akt.