Lycorine hydrochloride inhibits metastatic melanoma cell-dominant vasculogenic mimicry

Authors

  • Ruifang Liu,

    1.  Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China
    2.  Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China
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    • These authors contributed equally to this work.

  • Zhifei Cao,

    1.  Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China
    2.  Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China
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    • These authors contributed equally to this work.

  • Jian Tu,

    1.  Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China
    2.  Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China
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  • Yanyan Pan,

    1.  Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China
    2.  Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China
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  • Bingxue Shang,

    1.  Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China
    2.  Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China
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  • Gaochuan Zhang,

    1.  Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China
    2.  Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China
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  • Meimei Bao,

    1.  Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China
    2.  Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China
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  • Shasha Zhang,

    1.  Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China
    2.  Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China
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  • Ping Yang,

    1.  Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China
    2.  Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China
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  • Quansheng Zhou

    1.  Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China
    2.  Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China
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Q. Zhou, e-mail: quanshengzhou@yahoo.com

Summary

Melanoma cells actively participate in tumor angiogenesis and vasculogenic mimicry. However, anti-angiogenic therapy in patients with melanoma has not shown a significant survival gain. Thus, new anti-melanoma angiogenic and vasculogenic drugs are highly desired. Using the metastatic melanoma cell line C8161 as a model, we explored melanoma vasculogenic inhibitors and found that lycorine hydrochloride (LH) effectively suppressed C8161 cell-dominant formation of capillary-like tubes in vitro and generation of tumor blood vessels in vivo with low toxicity. Mechanistic studies revealed that LH markedly hindered expression of VE-cadherin in C8161 cells, but did not affect expression of six other important angiogenic and vasculogenic genes. Luciferase assays showed that LH significantly impeded promoter activity of the VE-cadherin gene in a dose-dependent manner. Together, these data suggest that LH inhibits melanoma C8161 cell-dominant vasculogenic mimicry by reducing VE-cadherin gene expression and diminishing cell surface exposure of the protein.

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