Inhibition of tumor angiogenesis by TTF1 from extract of herbal medicine

Inhibition of tumor angiogenesis by TTF1 from extract of herbal medicine
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草药提取物中 TTF1 对肿瘤血管生成的抑制作用

DOI:
10.3748/wjg.v17.i44.4875
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发表时间:
2011-11-28
影响因子:
4.3
通讯作者:
Zhang, Xue-Wu
Zhang, Xue-Wu
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Chao;Li, Xiao-Wan;Zhang, Xue-Wu

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目的:研究从珍珠梅提取物中分离得到的5,2,4‘-三羟基-6,7,5’-三甲氧基黄酮(TTF1)对肿瘤血管生成的抑制作用。采用Weidner毛细血管计数法对组织切片进行CD34免疫组织化学染色,测定微血管密度(MVD)。采用实时定量聚合酶链式反应和Western blotting检测血管内皮细胞生长因子(VEGF)、血管内皮生长因子受体2(VEGFR2,Flk-1/KDR)、碱性成纤维细胞生长因子(BFGF)、环氧合酶(COX)-2和缺氧诱导因子(HIF)-1α的mRNA和蛋白表达水平。结果:在25、50和100mU g/胚胎×5d处理组,TTF1对CAM的抑制率分别为30.8%、38.2%和47.5%。TTF1处理浓度为5、10和20mU/kg时,对肿瘤大小的抑制率分别为43.8%、49.4%和59.6%。TTF1处理浓度为5mU/kg、10mU/kg和20mU/kg时,平均微血管密度分别为14.2、11.2和8.5。结论:TTF1可抑制肿瘤血管生成,其机制可能与下调VEGF、KDR、bFGF、HIF-1α和COX-1α的表达有关。(C)2011年白石登。版权所有。
AIM: To study the inhibition of tumor angiogenesis by 5,2,4'-trihydroxy-6,7,5'-trimethoxyflavone (TTF1) isolated from an extract of herbal medicine Sorbaria sorbifolia.METHODS: Angiogenic activity was assayed using the chick embryo chorioallantoic membrane (CAM) method. Microvessel density (MVD) was determined by staining tissue sections immunohistochemically for CD34 using the Weidner capillary counting method. The mRNA and protein levels of vascular endothelial growth factor (VEGF), vascular endothelialgrowth factor receptor 2 (VEGFR2, Flk-1/KDR), basic fibroblast growth factor (bFGF), cyclo-oxygenase (COX)-2 and hypoxia-inducible factor (HIF)-1 alpha were detected by quantitative real-time polymerase chain reaction and Western blotting analysis.RESULTS: The TTF1 inhibition rates for CAM were 30.8%, 38.2% and 47.5% with treatment concentrations of 25, 50 and 100 mu g/embryo x 5 d, respectively. The inhibitory rates for tumor size were 43.8%, 49.4% and 59.6% at TTF1 treatment concentrations of 5, 10, and 20 mu mol/kg, respectively. The average MVD was 14.2, 11.2 and 8.5 at treatment concentrations of 5 mu mol/kg, 10 mu mol/kg and 20 mu mol/kg TTF1, respectively. The mRNA and protein levels of VEGF, KDR, bFGF, COX-2 and HIF-1 alpha in mice treated with TTF1 were significantly decreased.CONCLUSION: TTF1 can inhibit tumor angiogenesis, and the mechanism may be associated with the down-regulation of VEGF, KDR, bFGF, HIF-1 alpha and COX-2. (C) 2011 Baishideng. All rights reserved.