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

Banghua Wang; Jia Shen; Zexia Wang; Jian-Xia Liu; Zhifeng Ning; Meichun Hu

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자료유형: 학술저널

저자정보: Banghua Wang (Hubei University of Science and Technology) Jia Shen (Chinese Academy of Sciences) Zexia Wang (Hubei University of Science and Technology) Jian-Xia Liu (Hubei University of Science and Technology) Zhifeng Ning (Hubei University of Science and Technology) Meichun Hu (Hubei University of Science and Technology)

저널정보: 한국유방암학회 Journal of Breast Cancer Journal of Breast Cancer Vol.21 No.1

발행연도: 2018.1

수록면: 11 - 20 (10page)

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Purpose: 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. Methods: A human breast cancer xenograft mouse model was used to investigate the efficacy of isomangiferin in vivo. The inhibitory effect of isomangiferin on breast cancer cells and the underlying mechanism were examined in vitro. Results: Isomangiferin suppressed tumor growth in xenografts. In vitro, 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, VEGFinduced activation of the VEGFR-2 kinase pathway was downregulated by isomangiferin. Conclusion: 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.

참고문헌 (29)

참고문헌 신청

Jandial R / 2017 / Operative and therapeutic advancements in breast cancer metastases to the brain / Clin Breast Cancer

Moreno AC / 2017 / Use of regional nodal irradiation and its association with survival for women with high-risk, early stage breast cancer: a national cancer database analysis / Adv Radiat Oncol 2:291~300

Santoni M / 2017 / Incidence and risk of cardiotoxicity in cancer patients treated with targeted therapies / Cancer Treat Rev 59:123~131

Zhou J / 2016 / VEGFR2-targeted three-dimensional ultrasound imaging can predict responses to antiangiogenic therapy in preclinical models of colon cancer / Cancer Res 76:4081~4089

Pan Y / 2015 / A preclinical evaluation of SKLB261, a multikinase inhibitor of EGFR/Src/VEGFR2, as a therapeutic agent against pancreatic cancer / Mol Cancer Ther 14:407~418

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