FTY720 induces apoptosis in B16F10-NEX2 murine melanoma cells, limits metastatic development in vivo, and modulates the immune system

Página do item simplificado
dc.contributor.authorPereira, Felipe Valença [UNIFESP]
dc.contributor.authorArruda, Denise Costa [UNIFESP]
dc.contributor.authorFigueiredo, Carlos Rogerio [UNIFESP]
dc.contributor.authorMassaoka, Mariana Hiromi [UNIFESP]
dc.contributor.authorMatsuo, Alisson Leonardo [UNIFESP]
dc.contributor.authorBueno, Valquiria [UNIFESP]
dc.contributor.authorRodrigues, Elaine Guadelupe [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2015-06-14T13:45:32Z
dc.date.available2015-06-14T13:45:32Z
dc.date.issued2013-07-01
dc.description.abstractOBJECTIVE: Available chemotherapy presents poor control over the development of metastatic melanoma. FTY720 is a compound already approved by the Food and Drug Administration for the treatment of patients with multiple sclerosis. It has also been observed that FTY720 inhibits tumor growth in vivo (experimental models) and in vitro (animal and human tumor cells). The aim of this study was to evaluate the effects of FTY720 on a metastatic melanoma model and in tumor cell lines. METHODS: We analyzed FTY720 efficacy in vivo in a syngeneic murine metastatic melanoma model, in which we injected tumor cells intravenously into C57BL/6 mice and then treated the mice orally with the compound for 7 days. We also treated mice and human tumor cell lines with FTY720 in vitro, and cell viability and death pathways were analyzed. RESULTS: FTY720 treatment limited metastatic melanoma growth in vivo and promoted a dose-dependent decrease in the viability of murine and human tumor cells in vitro. Melanoma cells treated with FTY720 exhibited characteristics of programmed cell death, reactive oxygen species generation, and increased β-catenin expression. In addition, FTY720 treatment resulted in an immunomodulatory effect in vivo by decreasing the percentage of Foxp3+ cells, without interfering with CD8+ T cells or lymphocyte-producing interferon-gamma. CONCLUSION: Further studies are needed using FTY720 as a monotherapy or in combined therapy, as different types of cancer cells would require a variety of signaling pathways to be extinguished.en
dc.description.affiliationUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina (EPM-UNIFESP) Departamento de Microbiologia, Imunologia e Parasitologia
dc.description.affiliationUnifespUNIFESP, EPM, (EPM-UNIFESP) Depto. de Microbiologia, Imunologia e Parasitologia
dc.description.sourceSciELO
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Pesquisa e Desenvolvimento (CNPq)
dc.description.sponsorshipID2008/51256-7
dc.format.extent1018-1027
dc.identifierhttp://dx.doi.org/10.6061/clinics/2013(07)21
dc.identifier.citationClinics. Faculdade de Medicina / USP, v. 68, n. 7, p. 1018-1027, 2013.
dc.identifier.doi10.6061/clinics/2013(07)21
dc.identifier.fileS1807-59322013000701018.pdf
dc.identifier.issn1807-5932
dc.identifier.scieloS1807-59322013000701018
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/7856
dc.identifier.wosWOS:000322601600021
dc.language.isoeng
dc.publisherFaculdade de Medicina / USP
dc.relation.ispartofClinics
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectFTY720en
dc.subjectMurine Melanoma B16F10en
dc.subjectApoptosisen
dc.subjectMetastasisen
dc.subjectReactive Oxygen Speciesen
dc.subject-Cateninen
dc.subjectImmunomodulationen
dc.titleFTY720 induces apoptosis in B16F10-NEX2 murine melanoma cells, limits metastatic development in vivo, and modulates the immune systemen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Pacote Original
Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
S1807-59322013000701018.pdf
Tamanho:
2.43 MB
Formato:
Adobe Portable Document Format
Descrição:
Baixar
Coleções
EPM - Artigos