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Antiangiogenic therapy with Nintedanib affects hypoxia, angiogenesis and apoptosis in the ventral prostate of TRAMP animals.
da Silva, Raquel Frenedoso; Banzato, Thais Petrochelli; Alves, Letícia Ferreira; Carvalho, João Ernesto; Agarwal, Rajesh; Cagnon, Valéria Helena Alves.
Afiliação
  • da Silva RF; Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, São Paulo, 13083-865, Brazil.
  • Banzato TP; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Alves LF; Chemical, Biological and Agricultural Pluridisciplinary Research Center, State University of Campinas (UNICAMP), São Paulo, Brazil.
  • Carvalho JE; Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, São Paulo, 13083-865, Brazil.
  • Agarwal R; Chemical, Biological and Agricultural Pluridisciplinary Research Center, State University of Campinas (UNICAMP), São Paulo, Brazil.
  • Cagnon VHA; Faculty of Pharmaceutical Sciences, State University of Campinas (UNICAMP), São Paulo, Brazil.
Cell Tissue Res ; 379(2): 407-420, 2020 Feb.
Article em En | MEDLINE | ID: mdl-31473819
The antiangiogenic therapy for prostate cancer with Nintedanib, a potent inhibitor of important growth factor receptors, has been proven to delay tumor progression and arrest tumor growth; thus, the aim herein is to evaluate Nintedanib effects on tumor cells, besides angiogenesis and apoptosis processes, metalloproteinases and hypoxia factor in an animal model. Nintedanib promoted growth inhibition and cell death in a dose-dependent manner, showing no tumor selectivity. 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 and 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 and HIF-1α and a significantly increased apoptosis of epithelial cells. Furthermore, late Nintedanib treatment decreased FGF-2, VEGFR-1 and FGFR-3 levels. Importantly, even after treatment discontinuation, treated animals displayed a significant decrease in VEGFR-1 as well as MMP-9. 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 the early stages of disease development. Nintedanib treatment has shown to be a promising approach for prostate cancer therapy, especially in the early stages of the disease, interfering in different carcinogenesis progression pathways.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Próstata / Neoplasias da Próstata / Adenocarcinoma / Apoptose / Inibidores da Angiogênese / Indóis / Hipóxia Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Cell Tissue Res Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Próstata / Neoplasias da Próstata / Adenocarcinoma / Apoptose / Inibidores da Angiogênese / Indóis / Hipóxia Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Cell Tissue Res Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha