Wang Banghua, Shen Jia, Wang Zexia, Liu Jianxia, Ning Zhifeng, Hu Meichun
Research Center of Basic Medical Sciences, School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning, China.
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
J Breast Cancer. 2018 Mar;21(1):11-20. doi: 10.4048/jbc.2018.21.1.11. Epub 2018 Mar 23.
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.
血管内皮生长因子（VEGF）信号转导主要依赖于其与血管内皮生长因子受体2（VEGFR - 2）的结合。VEGF下游信号蛋白介导其在癌症进展中的多种作用，包括对肿瘤生长、转移和血管形成的作用。VEGFR - 2信号的激活是乳腺癌的一个标志，被认为是乳腺癌的一个治疗靶点。在此，我们报告一项关于小分子异芒果苷对VEGFR - 2信号通路调控的研究。
使用人乳腺癌异种移植小鼠模型来研究异芒果苷的疗效。检测了异芒果苷对乳腺癌细胞的抑制作用及其潜在机制。
异芒果苷抑制异种移植瘤的生长。此外，异芒果苷处理抑制癌细胞的增殖、迁移、侵袭和黏附。异芒果苷对乳腺癌生长的影响与其对血管生成的抑制作用密切相关。大鼠主动脉环试验表明，异芒果苷在VEGF诱导的微血管芽生过程中显著抑制血管形成。此外，异芒果苷处理抑制VEGF诱导的人脐静脉内皮细胞增殖和毛细血管样结构的形成。机制上，异芒果苷诱导乳腺癌细胞发生半胱天冬酶依赖性凋亡。此外，异芒果苷下调VEGF诱导的VEGFR - 2激酶途径的激活。
我们的研究结果表明，异芒果苷通过功能性抑制VEGFR - 2发挥抗乳腺癌作用。异芒果苷在药学上靶向VEGFR - 2可能是一种有效的乳腺癌治疗策略。
