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目的:探讨趋化因子受体4(chemokine receptor 4,CXCR4)在神经胶质瘤中的表达及在血管生成中的作用。方法:通过免疫组化法检测正常或神经胶质瘤患者的瘤体组织标本CXCR4、血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达,其结果做方差分析及相关性分析;采用ELISA观察CXCR4的配体基质细胞衍生因子-1(stromal derived factor-1,SDF-1)对U87胶质瘤细胞系VEGF分泌的影响;同时利用多种处理方式(对照组、SDF-1处理组、CXCR4拮抗剂AMD3100处理组、CXCR4 RNA干扰处理组)作用于U87后,取其条件培养上清与人脐静脉内皮细胞系(human umbilical vein endothelial cells,HUVECs)共培养,比较小管样结构(tubule-like structure,TLS)生成数量的变化。结果:神经胶质瘤中CXCR4、VEGF的表达量随着肿瘤恶性度的升高而增加,且二者呈线性正相关(P<0.01)。ELISA实验表明SDF-1可通过CXCR4促进VEGF的分泌(P<0.01)。成管实验提示CXCR4与胶质瘤血管生成相关。结论:CXCR4与神经胶质瘤恶性度相关,且其配体SDF-1可通过CXCR4影响VEGF的表达,将CXCR4拮抗或干扰明显影响胶质瘤血管增生,提示CXCR4可能为神经胶质瘤的治疗提供相应靶点和思路。
Objective: To investigate the expression of chemokine receptor 4 (CXCR4) in glioma and its role in angiogenesis. Methods: The expressions of CXCR4 and VEGF in normal or glioma tissues were detected by immunohistochemistry. The results were analyzed by ANOVA and correlation analysis. CXCR4 ligand stromal derived factor-1 (SDF-1) on the secretion of VEGF in U87 glioma cell line; at the same time using a variety of treatment methods (control group, SDF-1 treatment group, CXCR4 Antagonist AMD3100 and CXCR4 RNA interference groups) were treated with U87. The conditioned medium was co-cultured with human umbilical vein endothelial cells (HUVECs), and the tubule-like structure, TLS) The number of changes generated. Results: The expression of CXCR4 and VEGF in glioma increased with the malignant degree of tumor, and the positive correlation was found between them (P <0.01). ELISA experiments showed that SDF-1 can promote the secretion of VEGF through CXCR4 (P <0.01). Tube formation experiments suggest that CXCR4 is associated with glioma angiogenesis. Conclusion: CXCR4 is associated with the malignancy of glioma, and its ligand SDF-1 can affect the expression of VEGF through CXCR4. The antagonism or interference of CXCR4 may significantly affect the proliferation of glioma, suggesting CXCR4 may be a treatment of glioma Provide the appropriate target and ideas.