Effects of Lipoxin A4 on CoCl2-Induced Angiogenesis and Its Possible Mechanisms in Human Umbilical Vein Endothelial Cells

Abstract

Lipoxin A₄ (LXA₄), a ‘stop signal’ for inflammation, is endogenously produced by eicosanoids, mainly via cell-to-cell interactions. At present, its influence on hypoxic angiogenesis, which is responsible for tumor growth and metastasis, has not been determined. Hypoxia regulates a variety of transcription factors including hypoxia-inducible factor (HIF)-1α, which plays a role in the expression of vascular endothelial growth factor (VEGF) and is considered a target for anti-angiogenic therapy. In this study, we utilized cobalt chloride (CoCl₂) to mimic hypoxia in vitro. Data suggested that LXA₄ decreased the expression and nucleus translocation of HIF-1α in a dose-dependent manner in CoCl₂-treated human umbilical vein endothelial cells (HUVEC). Furthermore, we confirmed that LXA₄ suppressed VEGF expression, tube formation and migration activity of HUVEC under hypoxia induced by CoCl₂. These results suggest that LXA₄ may have inhibitory effects on tumor angiogenesis through downregulation of the expression and nucleus translocation of HIF-1α. In summary, this study provides the first evidence for the anti-angiogenic role of LXA₄ on hypoxic human endothelial cells, which may have therapeutic value for cancer and other angiogenesis-associated diseases.