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

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.