Wogonoside Inhibits Angiogenesis in Breast Cancer Via Suppressing Wnt/β-Catenin Pathway
Wogonoside Inhibits Angiogenesis in Breast Cancer Via Suppressing Wnt/β-Catenin Pathway
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DOI：
10.1002/mc.22412
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发表时间：
2016-11-01
影响因子：
4.6
通讯作者：
Lu, Na
中科院分区：
文献类型：
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作者：
Huang, Yujie;Zhao, Kai;Lu, Na
汉黄芩苷是从黄芩中提取的黄酮类化合物，具有抗血管生成和抗白血病的作用。然而，它是否能抑制肿瘤血管生成尚不清楚。本研究旨在探讨汉黄芩苷对乳腺癌血管生成的抑制作用及其机制。ELISA检测表明，汉黄芩苷（25，50和100 μ M）降低MCF-7细胞VEGF的分泌分别为30.0%，35.4%和40.1%。我们发现它在体外和体内通过迁移、管形成、大鼠主动脉环和鸡胚绒毛尿囊膜（CAM）试验抑制MCF-7细胞条件培养基诱导的血管生成。汉黄芩苷能抑制MCF-7细胞裸鼠移植瘤的生长和血管生成。汉黄芩苷（80 mg/kg）和贝伐单抗（20 mg/kg）治疗组均能明显减轻肿瘤重量，抑瘤率分别为42.1%和48.7%。此外，机制研究表明汉黄芩苷抑制MCF-7细胞中Wnt/β-catenin通路的激活。汉黄芩苷（100mM）显著降低细胞内Wnt3a的水平，增加GSK-3 β、轴蛋白的表达，并促进β-连环蛋白的磷酸化以用于蛋白酶体降解。100mM汉黄芩苷对β-catenin在细胞核内的积累和β-catenin/TCF/Lef复合物的DNA结合活性的抑制率分别为49.2%和28.7%。总之，我们的研究结果表明，汉黄芩苷是一种潜在的肿瘤血管生成抑制剂，可以开发为乳腺癌的治疗剂。(C)2015 Wiley Periodicals，Inc.
Wogonoside, a main flavonoid component derived from the root of Scutellaria baicalensis Georgi, has been reported to have anti-angiogenesis and anti-leukemia activities. However, whether it can inhibit tumor angiogenesis is unclear. In this study, we investigate the inhibitory effect of wogonoside on angiogenesis in breast cancer and its underlying mechanisms. ELISA assay shows that wogonoside (25, 50, and 100 mu M) decreases the secretion of VEGF in MCF-7 cells by 30.0%, 35.4%, and 40.1%, respectively. We find it inhibits angiogenesis induced by the conditioned media from MCF-7 cells in vitro and in vivo by migration, tube formation, rat aortic ring, and chicken chorioallantoic membrane (CAM) assay. Meanwhile, wogonoside can inhibit the growth and angiogenesis of MCF-7 cells xenografts in nude mice. The reduction of tumor weight can be found both in wogonoside (80 mg/kg) and bevacizumab (20 mg/kg) treated group, and the tumor inhibition rate is 42.1% and 48.7%, respectively. In addition, mechanistic studies demonstrate that wogonoside suppresses the activation of Wnt/beta-catenin pathway in MCF-7 cells. Wogonoside (100mM) decreases the intracellular level of Wnt3a, increases the expression of GSK-3 beta, AXIN, and promotes the phosphorylation of beta-catenin for proteasome degradation significantly. Furthermore, the nuclear accumulation of beta-catenin and the DNA-binding activity of beta-catenin/TCF/Lef complex are inhibited by 49.2% and 28.7%, respectively, when treated with 100mM wogonoside. Taken together, our findings demonstrate that wogonoside is a potential inhibitor of tumor angiogenesis and can be developed as a therapeutic agent for breast cancer. (C) 2015 Wiley Periodicals, Inc.