Isomangiferin, a Novel Potent Vascular Endothelial Growth Factor Receptor 2 Kinase Inhibitor, Suppresses Breast Cancer Growth, Metastasis and Angiogenesis

• Published in: Journal of breast cancer 2018, 21(1), 85, pp.11-20
• Main Authors: Wang, Banghua, Shen, Jia, Wang, Zexia, Liu, Jianxia, Ning, Zhifeng, Hu, Meichun
• Format: Article
• Language: English
• Subjects: Original; 일반외과학
• ISSN: 1738-6756; 2092-9900
• DOI: 10.4048/jbc.2018.21.1.11

Vascular endothelial growth factor (VEGF) signal transduction mainly depends on its binding to VEGF receptor 2 (VEGFR-2). VEGF downstream signaling proteins mediate several of its effects in cancer progression, including those on tumor growth, metastasis, and blood vessel formation. The activation of VEGFR-2 signaling is a hallmark of and is considered a therapeutic target for breast cancer. Here, we report a study of the regulation of the VEGFR-2 signaling pathway by a small molecule, isomangiferin. A human breast cancer xenograft mouse model was used to investigate the efficacy of isomangiferin . The inhibitory effect of isomangiferin on breast cancer cells and the underlying mechanism were examined . Isomangiferin suppressed tumor growth in xenografts. , isomangiferin treatment inhibited cancer cell proliferation, migration, invasion, and adhesion. The effect of isomangiferin on breast cancer growth was well coordinated with its suppression of angiogenesis. A rat aortic ring assay revealed that isomangiferin significantly inhibited blood vessel formation during VEGF-induced microvessel sprouting. Furthermore, isomangiferin treatment inhibited VEGF-induced proliferation of human umbilical vein endothelial cells and the formation of capillary-like structures. Mechanistically, isomangiferin induced caspase-dependent apoptosis of breast cancer cells. Furthermore, VEGF-induced activation of the VEGFR-2 kinase pathway was down-regulated by isomangiferin. Our findings demonstrate that isomangiferin exerts anti-breast cancer effects via the functional inhibition of VEGFR-2. Pharmaceutically targeting VEGFR-2 by isomangiferin could be an effective therapeutic strategy for breast cancer.