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Low dosage of arsenic trioxide (As2O3) inhibits angiogenesis in epithelial ovarian cancer without cell apoptosis

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Abstract

Arsenic trioxide (As2O3) induces cell apoptosis and reduces the invasive and metastatic activities in various cancer types. However, the role of As2O3 in ovarian cancer angiogenesis remains unclear. In this study, we investigated the role of As2O3 in ovarian cancer angiogenesis and found that a low concentration of As2O3 causes no effects on epithelial ovarian cancer cell viability or apoptosis. Moreover, we found that As2O3-treated epithelial ovarian cancer cells demonstrate a reduced tube formation of endothelial cells in Matrigel. In addition, As2O3-treated epithelial ovarian cancer cells show a decreased VEGFA, VEGFR2 and CD31 mRNA expression. As per the underlying mechanisms involved in As2O3 treatment, we found that As2O3 inhibits VEGFA and VEGFR2 expression that thereby inhibits the VEGFA–VEGFR2–PI3K/ERK signaling pathway. This leads to a suppression in both VEGFA synthesis and angiogenesis-related gene expression. A decreased VEGFA synthesis and secretion also inhibits the VEGFA–VEGFR2–PI3K/ERK signaling pathway in human umbilical vein endothelial cells (HUVECs). In summary, our results may provide strategies for the use of As2O3 in the prevention of tumor angiogenesis.

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Funding

This work was supported by Faculty Start-up Funds of Jining Medical University (No. 600640001 to W Shen.), Shandong Medical Science and Technology Program (No. 2017WS144 to W Shen.) and Guizhou Traditional Chinese Medicine & National Medicine Science and Technology Research Program (No. QZYY2017-20 to D Luo).

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Authors and Affiliations

  1. The First People’s Hospital of Zunyi, Zunyi, 563002, China

    Dehong Luo, Yi Li, Rui Chen & Daishun Liu

  2. Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining, 272067, China

    Xiaoyuan Zhang, Yonghua Bao, Wancai Yang & Wenzhi Shen

  3. Department of Immunology, School of Medicine, Nankai University, Tianjin, 300071, China

    Renle Du, Wenjuan Gao & Na Luo

  4. Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Science and Peking Union Medical College, Beijing, 100021, China

    Shuangtao Zhao

  5. Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China

    Hui Wang

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  1. Dehong Luo
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  2. Xiaoyuan Zhang
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  3. Renle Du
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Correspondence to Daishun Liu or Wenzhi Shen.

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Luo, D., Zhang, X., Du, R. et al. Low dosage of arsenic trioxide (As2O3) inhibits angiogenesis in epithelial ovarian cancer without cell apoptosis. J Biol Inorg Chem 23, 939–947 (2018). https://doi.org/10.1007/s00775-018-1595-z

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  • DOI: https://doi.org/10.1007/s00775-018-1595-z

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