Abstract

N-methyl-N-nitrosourea (MNU) is a prevalent environmental carcinogen, which leads to tumors in various organs in animal models, while the mechanisms involved were still not fully understood. It is well known that anomalous angiogenesis is a key step in tumorigenesis and progression. In this study, we found that MNU induced abnormal angiogenesis which was accompanied by upregulation of rspo1 , p53 and vegfaa in zebrafish embryos. Moreover, it revealed that MNU-induced ectopic sprouting of blood vessels was significantly reduced in rspo1 -knockdown but not p53 -knockdown embryos, indicating that rspo1 was necessary for MNU-induced abnormal angiogenesis. Additionally, pharmaceutical activation or inhibition of Wnt/β-catenin signaling pathway using (2'Z,3'E)− 6-bromoindirubin-3'-oxime or CCT036477 significantly increased or inhibited the pro-angiogenic effect of MNU on developing zebrafish embryos, which was confirmed by the effect of proliferation and migration in MNU-treated bEnd.3 cells. These data together indicated that rspo1/Wnt/β-catenin/vegfaa axis is involved in the modulation of MNU-induced anomalous angiogenesis.