title: Roxarsone induces angiogenesis via PI3K/Akt signaling.
abstract: BACKGROUND
  3-Nitro-4-hydroxy phenyl arsenic acid, roxarsone, is widely used as an organic arsenic feed additive for livestock and poultry, which may increase the level of arsenic in the environment and the risk of exposure to arsenic in human. Little information is focused on the angiogenesis roxarsone-induced and its mechanism at present. This paper aims to study the role of PI3K/Akt signaling in roxarsone-induced angiogenesis in rat vascular endothelial cells and a mouse B16-F10 melanoma xenograft model.
  
  
  RESULTS
  The results showed that treatment with 0.1-10.0 µmol/L roxarsone resulted in an increase in the OD rate in the MTT assay, the number of BrdU-positive cells in the proliferation assay, the migration distance in the scratch test and the number of meshes in tube formation assay. Further, treatment with 1.0 µmol/L roxarsone was associated with significantly higher phosphorylation of PI3K/Akt and expression of VEGF than the control treatment. The PI3K inhibitor was found to significantly combat the effects of 1.0 µmol/L roxarsone. Furthermore, roxarsone treatment was observed to increase the weight and volume of B16-F10 xenografts and VEGF expression and PI3K/Akt phosphorylation in a dose-dependent manner, with the 25 mg/kg dose having significant effects.
  
  
  CONCLUSIONS
  These results demonstrate that roxarsone has the ability to promote growth and tube formation in vascular endothelial cells and the growth of mouse B16-F10 xenografts. Further, the findings also indicate that PI3K/Akt signaling plays a regulatory role in roxarsone-induced angiogenesis in vivo and in vitro.
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, 12# Wenhui East Road, Yangzhou, 225009 Jiangsu China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, 12# Wenhui East Road, Yangzhou, 225009 Jiangsu China.
authors.forename: Donglai
authors.initials: D
authors.lastname: Yin
authors.affiliation: Department of Veterinary Internal Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, 12# Wenhui East Road, Yangzhou, 225009 Jiangsu China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, 12# Wenhui East Road, Yangzhou, 225009 Jiangsu China.
authors.forename: Lingmin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, 12# Wenhui East Road, Yangzhou, 225009 Jiangsu China ; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Zhang
keywords: Angiogenesis; B16–F10 xenograft model; PI3K/Akt signaling; Roxarsone; Vascular endothelial cell