title: Organoarsenic Roxarsone Promotes Angiogenesis In Vivo.
abstract: Roxarsone, an organoarsenic feed additive, is widely used worldwide to promote animal growth. It has been found to exhibit a higher angiogenic index than As(III) at lower concentrations and to promote angiogenic phenotype in human endothelial cell in vitro. Little research has focused on the potential angiogenic effect of roxarsone in vitro or in vivo. Here, we investigated the pro-angiogenic effect of roxarsone in vivo. The effects of 0.1-10.0 μM roxarsone were tested in the rat endothelial cell Matrigel plug assay, chicken chorioallantoic membrane (CAM) model and MCF-7 cell xenograft tumour model; 10 ng/mL vascular endothelial growth factor (VEGF) was used as a positive control and PBS as a negative control. Roxarsone significantly increased the volume, weight and haemoglobin content of the Matrigel plugs compared to PBS group (p < 0.05); 1.0 μM roxarsone exerted the most significant effects. H&E staining and CD31 immunochemistry revealed obviously more new vessels or capillary-like structures in the plugs of the roxarsone and VEGF groups. Roxarsone significantly increased the numbers of primary/secondary vessels and area of vessels in the CAM assay and obviously increased tumour weight and volume in the xenograft model compared to PBS (p < 0.05). Histochemistry indicated local necrosis was observed at the centre of the xenograft tumours in the PBS and roxarsone groups, with less necrosis apparent in the VEGF-treated tumours. The growth of endothelial cells and VEGF level was obviously affected at blockade of VEGF and its receptor Flt-1/Flk-1 by SU5416 or its antibody in vitro. This study demonstrates roxarsone promotes angiogenesis in vivo, and a VEGF/VEGFR mechanism may be involved.
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou 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
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou 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, Yangzhou Jiangsu, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou Jiangsu, China.
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xin
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou Jiangsu, China.
authors.forename: Weibo
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou Jiangsu, China.|Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
authors.forename: Jiaqiao
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007118:Immunoassay; D061986:MCF-7 Cells; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D012406:Roxarsone / Q000633:toxicity*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D042461:Vascular Endothelial Growth Factor A; D012406:Roxarsone