华蟾素调控VEGFVEGFR2信号传导抑制肿瘤血管生成研究.docVIP

华蟾素调控VEGFVEGFR2信号传导抑制肿瘤血管生成研究 　　摘 要：目的：探讨华蟾素注射液对肿瘤血管生成影响及其调控相关信号传导的分子机制。方法：采用Lewis肺癌荷瘤小鼠随机分为生理盐水组（阴性对照组）,参一组（阳性对照组）,华蟾素组，观察荷瘤小鼠肿瘤抑制率，瘤内微血管密度；采用免疫组化法检测VEGF表达；采用Western Blotting法检测人脐静脉血管内皮细胞VEGFR-2（KDR）表达。结果：华蟾素的抑瘤率在12％～31％；华蟾素能减少瘤内血管密度、降低瘤内VEGF表达及血管内皮细胞膜上VEGFR-2蛋白表达，华蟾素组与生理盐水组比较有显著差异（P0.05）。结论：华蟾素能抑制肿瘤血管生成，其作用机制与调控VEGF/VEGFR-2信号传导有关。 　　? 　　关键词：华蟾素；血管生成；信号传导；血管内皮生长因子? 　　中图分类号：R285.5 　　文献标识码：A文章编号： 　　1673-7717（2008）11-2489-03 　　?? 　　Mechanism Investigation of Huachansu in Regulating Signal Transduction of Tumor Angiogenesis 　　?? 　　LIU Hao，LIN Hong?sheng，HUA Bao?jin，LU Wen?ping? 　　（Ganganmen Hospital，China Academy of Chinese Medical Sciences, Beijing 100053,China 　　）?? 　　Abstract：Objective:To investigate the effect of Huachansu(HCS) on angiogenesis and the mechanism of which is regulation in signal transduction.Methods:Mice transplanted with Lewis lung cells were randomly divided into saline group (negative control), Rg3 group (positive control) and HCS group. The tumor inhibition rate and the quantity of microvessel density were observed; The expression of VEGF of implanted tumor of mice was tested by immunohistochemistry . The expression of VEGFR-2 of HUVECs was tested by western blotting method.Results:The results showed the tumor inhibited rates of HCS were 12%~31%. HCS reduced the quantity of microvessel density in tumor and lowered the expression of VEGF of tumor and VEGFR-2 ofHUVECs,HCS group was lower than those in the saline group, significant difference was shown in comparison with those in the saline group (P0.05).Conclusion:HCS could inhibit angiogenesis, the mechanism of which is the regulation of VEGF/ VEGFR-2 pathway. 　　? 　　Key words：HCS injection;angiogenesis;signal transduction;VEGF 　　?? 　　华蟾素注射液（HCS injection）是临床常用的治疗肿瘤中药注射剂，应用广泛，疗效确切，对其抗肿瘤作用以往有许多报道[1-2]，但在肿瘤血管生成方面尚未涉及。本文旨在探讨华蟾素对肿瘤血管生成作用及其信号传导机制的影响。? 　　1材料? 　　C57BL/6J纯系小鼠，购自中国医学科学院实验动物中心；Lewis肺癌瘤株购自中国医学科学院药物研究所；人脐静脉血管内皮细胞(HUVEC)株购自Cascade Biologics? 公司；华蟾素注射液由安徽金蟾药业公司提供；参一胶囊（Rg3）由吉林