• Open Access

Norcantharidin inhibits tumor angiogenesis via blocking VEGFR2/MEK/ERK signaling pathways

Authors

  • Long Zhang,

    1. Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    2. Interventional Cancer Institute of Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    3. Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
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    • These authors contributed equally to this work.

  • Qing Ji,

    1. Interventional Cancer Institute of Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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    • These authors contributed equally to this work.

  • Xuan Liu,

    1. Interventional Cancer Institute of Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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  • Xingzhu Chen,

    1. Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    2. Interventional Cancer Institute of Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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  • Zhaohua Chen,

    1. Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
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  • Yanyan Qiu,

    1. Interventional Cancer Institute of Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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  • Jian Sun,

    1. Interventional Cancer Institute of Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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  • Jianfeng Cai,

    1. Department of Chemistry, University of South Florida, Tampa, Florida, USA
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  • Huirong Zhu,

    Corresponding author
    • Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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  • Qi Li

    Corresponding author
    1. Interventional Cancer Institute of Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    • Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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To whom correspondence should be addressed:

E-mails: Lzwf@hotmail.com; zhu_huirong@126.com

Abstract

Norcantharidin (NCTD), the demethylated form of Cantharidin, a reagent isolated from blister beetles, has been shown to be an anti-tumor agent capable of inhibiting proliferation as well as inducing apoptosis in many cancer cell lines. However, little is known about the effect of NCTD in tumor angiogenesis. In this study, we demonstrated that NCTD inhibited vascular endothelial growth factor (VEGF)-induced cell proliferation, migration, invasion, and capillary tube formation of primary human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Furthermore, we showed NCTD inhibited tumor growth and angiogenesis of colon cancer cells (LOVO) in vivo. We then mechanistically described that NCTD specifically abrogated the phosphorylation/activation of vascular endothelial growth factor receptor-2 (VEGFR2)/MEK/ERK pathway kinases, with little effect on the phosphorylation of p38 MAPK and Akt, and on Cox-2 expression. In summary, our results indicate that NCTD is a potential inhibitor of tumor angiogenesis by blocking VEGFR2/MEK/ERK signaling.

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