ABSTRACT
The erythropoietin-producing hepatocellular receptor (Eph)B4 receptor is closely associa-ted with tumor growth and angiogenesis,which is over-expressed in a wide variety of tumors.Molecular probes targeted for EphB4 receptor can improve the accuracy and specificity of tumor diagnosis.A lot of molecular probes targeted for EphB4 receptor have been designed,which are expected to provide new means for the early diagnosis and therapeutics of tumors.
ABSTRACT
Objective To observe the effect of suramin combinated with PG-Rg3 on xenograft growth of lung adeno-carcinoma in mice, and the related mechanism thereof. Methods Forty C57BL/6J mice bearing Lewis cells were random-ized into five groups:control group, cisplatin (DDP) group, suramin group, PG-Rg3 group and combination group. Appropri-ate interventions were given in five groups of mice. Mice were sacrificed at day 24 after tumor inoculation. The subcutaneous tumors were stripped for histological examination. The tumor inhibitory rate was measured. The expressions of erythropoietin-producing hepatoma amplified sequences (Eph) B4 protein, Bcl-2 and tumors microvessel density (MVD) were determined by immunohistochemistry method with image analyze system. The apoptosis of tumor cells was measured by biotinyated dUTP nick and labeling (TUNEL) method. Results There were significantly lower values in subcutaneous tumor volume and weight in drug-treated groups than those in control group (P<0.05). The inhibitory rates were 39.20%, 49.11%, 54.86%and 62.49%in cisplatin group, suramin group, PG-Rg3 group and combined group (P<0.05). The values of EphB4, MVD and Bcl-2 grey values were significantly decreased, the apoptotic index was significantly increased, in suramin group, PG-Rg3 group and combined group than those of control group and DDP group (P<0.05). The values of EphB4, MVD and Bcl-2 grey values were significantly increased, the apoptotic index was significantly decreased, in suramin group and PG-Rg 3 group than those of combined group (P<0.05). Conclusion Suramin combinated with PG-Rg3 can produce a synergetic inhibitory activity against tumor growth of lung adenocarcinoma, which may be associated with the effect of suppressing the expression of EphB4 and angiogenesis, and the promotion of tumor cell apoptosis.
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Objective: To determine the interfering effects of EphB4-targeted short interfering RNA (siRNA) on EphB4 mRNA expression and its effect on the growth of glioma U251 cell line. Method: EphB4-targeted siRNA was designed and synthesized, and then was transfected into U251 cells. The inhibition of EphB4 mRNA expression was detected by RT-PCR. The effect of EphB4-targeted siRNA on cell growth rate was measured by CCK-8 method. Cell apoptosis was tested by flow cytometry (FCM). Wound healing test was used to observe the migration ability of cells. The invasiveness of tumor cells was evaluated by counting the number of cells passing the Transwell membrane. Results: EphB4 mRNA transcription level was decreased by 75.0% after transfection of malignant glioma U251 cells with 100 nmol/L siRNA-EphB4. The inhibition of cell proliferation was in a dose-dependent manner. FCM analysis showed that cells were arrested at sub-G1 phase at different degrees and the migration capacity decreased after transfection with 100 nmol/L siRNA-EphB4 compared with the negative control. The number of cells permeating the matrigel membrane significantly were decreased in the siRNA-EphB4 transfection group compared with the control group. Conclusion: siRNA-EphB4 markedly targetes and knocks down EphB4 gene transcription. Down-regulation of EphB4 affects cell proliferation and induces apoptosis of cells. Transfection of siRNA-EphB4 into U251 cells inhibits the migration and invasion abilities of cells at various degrees. It indicates that silencing EphB4 expression might become a noval approach in the treatment of glioma.
ABSTRACT
Objective To investigate the expressions of EphB4 receptor and hypoxia inducible factor 1? (HIF-1?) protein in human primary gastric carcinoma, and to study the biological implication of their expression. Methods The expressions of EphB4 receptor and HIF-1? protein were detected in 74 specimens of human primary gastric carcinoma (gastric carcinoma group) and in 13 normal gastric mucosa tissues (control group) by immunohistochemistry. Correlations between the expression of these proteins, and clinical and pathological features were respectively analyzed. Result High expressions of EphB4 receptor and HIF-1? protein were found to be 62.2% (46/74) and 52.7% (39/74) respectively in gastric carcinoma group, while the expressions of EphB4 receptor and HIF-1? protein in control group were 15.38% (2/13) and 0% (0/13), respectively. The differences were significant between two grrups (P