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Type: Artigo
Title: Antiangiogenic therapy with Nintedanib affects hypoxia, angiogenesis and apoptosis in the ventral prostate of TRAMP animals
Author: Silva, Raquel Frenedoso
Banzato, Thais Petrochelli
Ferreira, Leticia Alves
Carvalho, João Ernesto
Agarwal, Rajesh
Cagnon, Valéria Helena Alves
Abstract: The antiangiogenic therapy for prostate cancer with Nintedanib, a potent inhibitor of important growth factors receptors, has been proven to delay tumor progression and arrest tumor growth
thus, the aim herein was to evaluate Nintedanib efficacy on angiogenesis and apoptosis processes, metalloproteinases and hypoxia factor. Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) were treated with Nintedanib (10 mg/Kg/day) in different stages of tumor development and the ventral prostate was examined for protein levels by means of immunohistochemistry and Western Blotting, besides apoptosis evaluation. In vitro antiproliferative activity of Nintedanib was also assessed in nine human tumor cell lines. Early Nintedanib treatment has shown decreased levels of FGF-2, VEGFR-1, MMP-9, HIF-1α, besides significantly increased apoptosis of epithelial cells. Furthermore, late Nintedanib treatment has decreased FGF-2, VEGFR-1 and FGFR-3 levels. Importantly, even after treatment discontinuation, treated animals display significant decrease in VEGFR-1 as well as MMP-9. Nintedanib promoted growth inhibition and cell death in a dosedependent manner, showing no tumor selectivity. Although Nintedanib treatment in late stages of tumor growth has shown some good results, it is noteworthy that the drug presents the best tissue response when administered in early stages of the disease development. Nintedanib treatment has shown to be a promising approach for prostate cancer therapy, especially in early stages of the disease, interfering in different carcinogenesis progression pathways
Subject: Neovascularização
Substâncias de crescimento
Próstata - Câncer
Country: Estados Unidos
Editor: Springer
Rights: fechado
Identifier DOI: 10.1007/s00441-019-03091-x
Date Issue: 2019
Appears in Collections:IB - Artigos e Outros Documentos

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