Roxarsone induces angiogenesis via PI3K/Akt signaling

Abstract

Background3-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.ResultsThe 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.ConclusionsThese 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.

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“…Based on data obtained from the aforementioned experiments, we conclude that P2X7R expressed on PDLSCs plays a positive role in PDLSC osteogenic differentiation under inflammatory conditions. To further explore the mechanism underlying P2X7R-induced PDLSC osteogenesis, we used qRT-PCR to evaluate 14 osteogenesis-related genes from the MAPK 18,37,51,52 , Wnt/β-catenin 12,14–16 and PI3K-AKT 13,53,54 families in P2X7R-overexpressing PDLSCs, genes that were previously reported to be related to PDLSC osteogenesis. We excluded Wnt-3 α because it exhibited relatively stable expression irrespective of the incubation conditions, and another three genes ( AP-1 , GSK-3β , and CTNNB ) were excluded because their expression levels were not significantly altered by inflammatory factors.…”

RETRACTED ARTICLE: MicroRNA-9 modified bone marrow-derived mesenchymal stem cells (BMSCs) repair severe acute pancreatitis (SAP) via inducing angiogenesis in rats

“…Tissue regeneration associated with anti- and pro-angiogenic signaling pathways mainly depends on the formation of new blood vessels, which is mediated by a complex process [ 7 ]. The PI3K/AKT signaling pathway, which can promote the proliferation and migration of VECs to trigger angiogenesis, has been investigated extensively [ 8 – 10 ]. Conversely, the VE-cadherin-catenin complex can strongly stabilize endothelial junctions against the migration of VECs, which can inhibit angiogenesis [ 11 – 13 ].…”

PI3K/Akt/mTOR Signaling Pathway and the Biphasic Effect of Arsenic in Carcinogenesis

“…In addition to bronchial epithelial cells, mouse epidermis-derived mouse epidermis-derived cells JB6Cl41, as well as normal human bladder SV-HUC-1 and A375 cells, all demonstrated activated PI3K and AKT activity after arsenic exposure ( Ouyang et al, 2006 ; Wang, 2013 ; Li et al, 2015 ). In vivo experiments treating Wistar rats and C57BL/6 mice with 1.0 μ mol/liter of roxarsone revealed activated PI3K and AKT phosphorylation in the vascular endothelial cells ( Wang et al, 2016 ). In fact, both acute and chronic arsenic treatments promoted PI3K/AKT phosphorylation.…”

“…In a study using both NB4 and gastric cancer cells, after the initial 4-hour ATO treatment, AKT phosphorylation heightened but decreased again after 16–24 hours of treatment ( Li et al, 2009 ). The controversial biologic effect of arsenic, and hence its biphasic effect on carcinogenesis, may depend on the type of compound and strength of exposure ( Wang et al, 2016 ).…”