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Organoarsenic Roxarsone Promotes Angiogenesis In Vivo
Author(s) -
Zhang Yumei,
Wang Yujing,
Lu Qianqian,
Xin Wenfang,
Cui Weibo,
Zhu Jiaqiao
Publication year - 2016
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12501
Subject(s) - matrigel , in vivo , angiogenesis , cd31 , chorioallantoic membrane , endothelial stem cell , vascular endothelial growth factor , chemistry , biology , andrology , in vitro , medicine , cancer research , biochemistry , vegf receptors , microbiology and biotechnology
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 CD 31 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 SU 5416 or its antibody in vitro . This study demonstrates roxarsone promotes angiogenesis in vivo, and a VEGF / VEGFR mechanism may be involved.