沙苑子黄酮对肿瘤血管形成的影响  

Effect of Flavonoids of Astragalus complanatus on Angiogenesis in Tumor

作　　者：胡延维[1] 张健[1] 刘春宇[1] 吴文倩[1] 

机构地区：[1]苏州大学医学部药学院,江苏苏州215123

出　　处：《中国药学杂志》2009年第19期1478-1482,共5页Chinese Pharmaceutical Journal

基　　金：江苏省高校自然科学基础研究项目(06KJB360105)

摘　　要：目的观察沙苑子黄酮(FAC)对肿瘤血管形成的影响,并探讨其作用机制。方法采用四甲基偶氮唑盐蓝(MTT)法观察正常条件培养基和肿瘤条件培养基下FAC对细胞ECV304增殖的作用;采用鸡胚绒毛尿囊膜(CAM)模型和裸鼠移植瘤组织微血管密度(MVD)分析,观察FAC对肿瘤新血管生成的影响;采用免疫组织化学方法观察FAC对裸鼠肿瘤组织血管生成因子(VEGF)及其受体Flt-1、Flk-1/KDR、Flt-4和血管生成抑制因子内皮抑素(ES)蛋白表达的影响。结果FAC对经人肝癌SMMC-7721细胞上清液处理的血管内皮细胞增殖有较明显的抑制作用,而对正常状态下的血管内皮细胞毒性较低;FAC明显抑制CAM新生血管生成,FAC-a(400 mg.L-1)组的血管指数为67.5%;裸鼠移植瘤MVD和VEGF及其受体Flt-1和Flk-1/KDR的蛋白表达明显降低,ES的蛋白表达显著增强。结论FAC可抑制肿瘤组织血管形成,其作用机制与下调VEGF及其受体的表达和上调ES的表达有关。OBJECTIVE To observe the inhibitory effect of flavonoids from Astragalus complanatus （FAC） on angiogenesis in tumor and its mechanism. METHODS The proliferation of endothelial cell ECV304 of human umbilical vein was evaluated in normal ECV304 cells and in ECV304 cells treated with tumor-secreted factors by MTT assay. The chick chorioallantoic membrane （CAM） test and microvascular density （MVD） tissues were used to investigate the inhibitory effect of FAC on tumor angiogenesis. The tumor tissue was stained by immunohistochemical method to detect the protein expressions of vascular endothelial growth factor （VEGF）, VEGFR1/FIt-1, VEGFR2/KDR/Flk-1, VEGFR3/Flt-4 aad endostatin （ES）. RESULTS FAC induced the enhancement of toxicity against ECV304 in the presence of tumor-secreted factors （P〈0.01） , strongly inhibited the angiogenesis in the chick chorioallantoic membrane（P 〈0.01 ） , significantly reduced the protein expression of VEGF, Flt- 1 and Flk- 1 in the tumor tissues（P 〈 0.01 ） , significantly enhanced the protein expression of ES（P〈0.01）. CONCLUSION FAC has dramatically inhibition effect on angiogenesis in tumor and its mechanism may be associated with the protein expressions ofVEGF, Flt-1, Flk-1 and ES.

关 键 词：沙苑子黄酮 肿瘤血管形成 ECV304细胞 血管内皮细胞生长因子 内皮抑素 

分 类 号：R965[医药卫生—药理学]