大豆苷元对乳腺癌生长和血管生成的影响

Effect of daidzein on the growth and angiogenesis of breast carcinoma

目的:利用7,12-二甲基苯蒽(DMBA)诱导的大鼠乳腺癌模型,探讨大豆苷元对乳腺癌肿瘤血管生成的抑制作用及机制。方法:建立DMBA诱导的乳腺癌大鼠模型,随机分为对照组、10、25、50和75 mg/kg大豆苷元灌胃组,观察各组肿瘤生长情况,测定肿瘤微血管密度(MVD),并计算各组肿瘤的增殖指数和凋亡指数;酶联免疫吸附试验(ELISA)法检测心脏离心血标本中血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(b FGF)和内皮抑素的水平。结果:与对照组比较,50和75 mg/kg大豆苷元组大鼠瘤体质量显著减轻(P<0.05),75 mg/kg大豆苷元组的凋亡指数增加,其抑制肿瘤血管生成的效果显著(均<0.05)。与对照组比较,25、50和75mg/kg大豆苷元组的VEGF水平降低,且呈剂量依赖性(P<0.05),同时50和75 m g/kg大豆苷元组的内皮抑素水平增加,差异均有统计学意义(P均<0.05)。结论:较高剂量(≥50 m g/kg)的大豆苷元能使大鼠乳腺肿瘤的微血管密度下降,可有效抑制乳腺肿瘤生长。

OBJECTIVE：To evaluate the inhibitory effects of daidzein on angiogenesis ofbreastcarcinoma,and to study their anti-cancer mechanisms by using the model of 7,12-dimethylbenz[α]anthraxcene （DMBA）-inducedbreast carcinoma in SD rats.METHODS：The DMBA -treated SD rats were randomly divided into control,10,25,50 and 75 mg/kg daidzein-gavaged groups. The growth of tumors was assessed in each group. The tumor microvessel density （MVD） was determined,and tumor proliferation index and apoptosis index were calculated. Moreover,vascular endothelial growth factor （VEGF）,basic fibroblast growth factor （bFGF） and endostatin levels were measured by ELISA. RESULTS：Compared with the control group,tumor mass was reduced more significantly in the 50 and 75 mg/kg daidzein groups （P〈0.05）. The apoptosis index of 75 mg/kg daidzein group was increased,and the effect of inhibiting tumor angiogenesis was significant （allP〈0.05）. Compared with the control group,the VEGF levels of 25,50 and 75 mg/kg daidzein groups were all decreased,in a dose-dependent manner（P〈0.05）,meanwhile endostatin levelswere increased in the 50 and 75 mg/kg daidzein groups,and the differences were statistically significant （allP〈0.05）. CONCLUSION： Higher dose of daidzein （≥50 mg/kg） could decrease MVD of mammary tumor and inhibit the growth of breast carcinoma effectively in rats.