Effects of lipoxin A(4) on CoCl(2)-induced angiogenesis and its possible mechanisms in human umbilical vein endothelial cells.
Lipoxin A(4) (LXA(4)), 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)-1alpha, 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 (CoCl(2)) to mimic hypoxia in vitro. Data suggested that LXA(4) decreased the expression and nucleus translocation of HIF-1alpha in a dose-dependent manner in CoCl(2)-treated human umbilical vein endothelial cells (HUVEC). Furthermore, we confirmed that LXA(4) suppressed VEGF expression, tube formation and migration activity of HUVEC under hypoxia induced by CoCl(2). These results suggest that LXA(4) may have inhibitory effects on tumor angiogenesis through downregulation of the expression and nucleus translocation of HIF-1alpha. In summary, this study provides the first evidence for the anti-angiogenic role of LXA(4) on hypoxic human endothelial cells, which may have therapeutic value for cancer and other angiogenesis-associated diseases.
Liu
Songjun
S
Department of Obstetrics and Gynecology, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.
Wu
Ping
P
Ye
Duyun
D
Huang
Yinping
Y
Zhou
Xiaoyan
X
Li
Yongsheng
Y
Cai
Lei
L
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D044045:Lipoxins / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D044045:Lipoxins; D042461:Vascular Endothelial Growth Factor A; C040527:lipoxin A4; D003035:Cobalt; C018021:cobaltous chloride