Low dosage of arsenic trioxide (As 2 O 3 ) inhibits angiogenesis in epithelial ovarian cancer without cell apoptosis.

Arsenic trioxide (As ₂ O ₃ ) induces cell apoptosis and reduces the invasive and metastatic activities in various cancer types. However, the role of As ₂ O ₃ in ovarian cancer angiogenesis remains unclear. In this study, we investigated the role of As ₂ O ₃ in ovarian cancer angiogenesis and found that a low concentration of As ₂ O ₃ causes no effects on epithelial ovarian cancer cell viability or apoptosis. Moreover, we found that As ₂ O ₃ -treated epithelial ovarian cancer cells demonstrate a reduced tube formation of endothelial cells in Matrigel. In addition, As ₂ O ₃ -treated epithelial ovarian cancer cells show a decreased VEGFA, VEGFR2 and CD31 mRNA expression. As per the underlying mechanisms involved in As ₂ O ₃ treatment, we found that As ₂ O ₃ 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 As ₂ O ₃ in the prevention of tumor angiogenesis.