Wogonoside inhibits angiogenesis in breast cancer via suppressing Wnt/β‐catenin pathway

作者: Yujie Huang , Kai Zhao , Yang Hu , Yuxin Zhou , Xuwei Luo

DOI: 10.1002/MC.22412

关键词: Tube formationCancer researchBiologyImmunologyChorioallantoic membraneScutellaria baicalensisCateninIn vitroAngiogenesisWnt signaling pathwayIn vivo

摘要: 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 inhibitory effect wogonoside on in breast cancer its underlying mechanisms. ELISA assay shows that (25, 50, 100 µM) decreases secretion VEGF MCF-7 cells by 30.0%, 35.4%, 40.1%, respectively. We find inhibits induced conditioned media vitro vivo migration, tube formation, rat aortic ring, chicken chorioallantoic membrane (CAM) assay. Meanwhile, growth xenografts nude mice. The reduction weight be found both (80 mg/kg) bevacizumab (20 mg/kg) treated group, inhibition rate 42.1% 48.7%, addition, mechanistic studies demonstrate suppresses activation Wnt/β-catenin pathway cells. Wogonoside (100 µM) intracellular level Wnt3a, increases expression GSK-3β, AXIN, promotes phosphorylation β-catenin for proteasome degradation significantly. Furthermore, nuclear accumulation DNA-binding activity β-catenin/TCF/Lef complex are inhibited 49.2% 28.7%, respectively, when with 100 µM wogonoside. Taken together, our findings potential inhibitor developed as therapeutic agent cancer. © 2015 Wiley Periodicals, Inc.

参考文章(50)
H. F. Dvorak, J. A. Nagy, D. Feng, L. F. Brown, A. M. Dvorak, Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis. Current Topics in Microbiology and Immunology. ,vol. 237, pp. 97- 132 ,(1999) , 10.1007/978-3-642-59953-8_6
Maria T. Valenti, Giuseppe Azzarello, Elena Balducci, Saverio Sartore, Marco Sandri, Riccardo Manconi, Umberto Sicari, Mario Bari, Orazio Vinante, Conditioned medium from MCF-7 cell line induces myofibroblast differentiation, decreased cell proliferation, and increased apoptosis in cultured normal fibroblasts but not in fibroblasts from malignant breast tissue. Histochemical Journal. ,vol. 33, pp. 499- 509 ,(2001) , 10.1023/A:1014927305775
Edurne Berra, Gilles Pagès, Jacques Pouysségur, MAP kinases and hypoxia in the control of VEGF expression. Cancer and Metastasis Reviews. ,vol. 19, pp. 139- 145 ,(2000) , 10.1023/A:1026506011458
Janusz Rak, Robert S. Kerbel, Ras regulation of vascular endothelial growth factor and angiogenesis. Methods in Enzymology. ,vol. 333, pp. 267- 283 ,(2001) , 10.1016/S0076-6879(01)33062-8
Jing Yao, Rong Hu, Jie Sun, Biqi Lin, Li Zhao, Yunying Sha, Binbin Zhu, Qi-Dong You, Tianhua Yan, Qing-Long Guo, Oroxylin A prevents inflammation-related tumor through down-regulation of inflammatory gene expression by inhibiting NF-κB signaling. Molecular Carcinogenesis. ,vol. 53, pp. 145- 158 ,(2014) , 10.1002/MC.21958
Xiuming Song, Yuxin Zhou, Mi Zhou, Yujie Huang, Zhiyu Li, Qidong You, Na Lu, Qinglong Guo, Wogonin influences vascular permeability via Wnt/β‐catenin pathway Molecular Carcinogenesis. ,vol. 54, pp. 501- 512 ,(2015) , 10.1002/MC.22093
George D. Yancopoulos, Samuel Davis, Nicholas W. Gale, John S. Rudge, Stanley J. Wiegand, Jocelyn Holash, Vascular-specific growth factors and blood vessel formation Nature. ,vol. 407, pp. 242- 248 ,(2000) , 10.1038/35025215
Hao Sun, Yong-jun Jiang, Qing-sen Yu, Cheng-cai Luo, Jian-wei Zou, The effect of Li+ on GSK-3 inhibition: Molecular dynamics simulation Journal of Molecular Modeling. ,vol. 17, pp. 377- 381 ,(2011) , 10.1007/S00894-010-0738-0
Marco Reis, Stefan Liebner, Wnt signaling in the vasculature. Experimental Cell Research. ,vol. 319, pp. 1317- 1323 ,(2013) , 10.1016/J.YEXCR.2012.12.023