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J Biol Inorg Chem. 2018 Aug;23(6):939-947. doi: 10.1007/s00775-018-1595-z. Epub 2018 Jul 16.

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

Author information

1
The First People's Hospital of Zunyi, Zunyi, 563002, China.
2
Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining, 272067, China.
3
Department of Immunology, School of Medicine, Nankai University, Tianjin, 300071, China.
4
Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Science and Peking Union Medical College, Beijing, 100021, China.
5
Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.
6
The First People's Hospital of Zunyi, Zunyi, 563002, China. ldsdoc@126.com.
7
Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining, 272067, China. shenwenzhi2011@126.com.

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.

KEYWORDS:

Angiogenesis; Apoptosis; As2O3; Epithelial ovarian cancer; VEGFA; VEGFR2

PMID:
30014256
DOI:
10.1007/s00775-018-1595-z

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