沙苑子黄酮对肿瘤血管形成的影响

 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。

Effect of Flavonoids of Astragalus complanatus on Angiogenesis in Tumor

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/Flt-1, VEGFR2/KDR/Flk-1, VEGFR3/Flt-4 and 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-1and 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 of VEGF, Flt-1, Flk-1 and ES.