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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 effect of FAC on tumor angiogenesis and to explore its mechanism. Methods MTT assay was used to observe the effect of FAC on the proliferation of ECV304 cells in normal condition and tumor-conditioned media. The chick chorioallantoic membrane (CAM) model and nude mice xenografts (MVD) to observe the effect of FAC on tumor angiogenesis. The expression of VEGF and its receptors Flt-1, Flk-1 / KDR, Flt-1 in tumor tissues of nude mice were observed by immunohistochemistry -4 and angiogenesis inhibitor endostatin (ES) protein expression. Results FAC had a significant inhibitory effect on the proliferation of human umbilical vein endothelial cells treated with human hepatocellular carcinoma SMMC-7721 cells, while the cytotoxicity to normal endothelial cells was lower. FAC-a (400 mg · L-1) group was 67.5%. The protein expression of MVD, VEGF, Flt-1 and Flk-1 / KDR in nude mice was significantly decreased and the protein expression of ES was significantly increased. Conclusion FAC can inhibit tumor angiogenesis and its mechanism is related to the down-regulation of the expression of VEGF and its receptor and the up-regulation of ES.