Efeito do TKI-258 sobre a motilidade de células de carcinoma epidermoide oral in vitro

Detalhes bibliográficos
Autor(a) principal: CARNEIRO, Anna Cecília Dias Maciel
Data de Publicação: 2016
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFTM
Texto Completo: http://bdtd.uftm.edu.br/handle/tede/771
Resumo: O carcinoma epidermoide oral é extremamente invasivo e este comportamento é regulado pela ligação de moléculas extracelulares aos receptores da membrana celular. Atualmente o bloqueio desses receptores com inibidores específicos constitui uma nova modalidade de tratamento para neoplasias. O TKI-258 inibe a autofosforilação dos receptores tirosina quinase: FGFRs, VEGFRs e PDGFRs. Este estudo visou avaliar o efeito do tratamento com TKI-258 sobre o movimento celular, utilizando a linhagem SCC-4 de carcinoma epidermoide oral humano. A F-actina foi evidenciada com rodamina conjugada à faloidina e os resultados foram analisados em microscopia confocal. Foram realizados ensaios tridimensionais de migração e invasão celular e as células controle e tratadas com TKI-258 foram contadas após 24 horas. As células controle apresentaram citoplasma abundante com ampla distribuição de F-actina e córtex celular evidente, porém as células tratadas com TKI-258 nas concentrações estudadas, apresentaram morfologia arredondada, citoplasma escasso, filamentos de actina desorganizados e córtex celular preservado. O tratamento com TKI-258 (1 μM, 5 μM e 10 μM) inibiu a migração celular de maneira concentraçãodependente (ANOVA, F=97,749, df=3, 10; p<0,0001). O número de células tratadas com TKI-258 (5 μM) que invadiram a membrana recoberta com MatrigelTM foi significativamente menor que das células controle (t=6.708; df=5; P<0,001). Os resultados obtidos demonstraram que o inibidor tirosina quinase TKI-258 exerce um efeito inibitório sobre o citoesqueleto de actina, migração e invasão celular e provavelmente estes processos são regulados pelas via de sinalização: FGFRs e/ou do PDGFRs e/ou VEGFRs.
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spelling Efeito do TKI-258 sobre a motilidade de células de carcinoma epidermoide oral in vitroInvasão celular.Migração celular.Movimento celular.Carcinoma de células escamosas.TKI-258.Inibidor tirosina quinase.Cell invasion.Cell migration.Cell movement.Squamous cell carcinoma.TKI-258.Tyrosine kinase inhibitor.MorfologiaO carcinoma epidermoide oral é extremamente invasivo e este comportamento é regulado pela ligação de moléculas extracelulares aos receptores da membrana celular. Atualmente o bloqueio desses receptores com inibidores específicos constitui uma nova modalidade de tratamento para neoplasias. O TKI-258 inibe a autofosforilação dos receptores tirosina quinase: FGFRs, VEGFRs e PDGFRs. Este estudo visou avaliar o efeito do tratamento com TKI-258 sobre o movimento celular, utilizando a linhagem SCC-4 de carcinoma epidermoide oral humano. A F-actina foi evidenciada com rodamina conjugada à faloidina e os resultados foram analisados em microscopia confocal. Foram realizados ensaios tridimensionais de migração e invasão celular e as células controle e tratadas com TKI-258 foram contadas após 24 horas. As células controle apresentaram citoplasma abundante com ampla distribuição de F-actina e córtex celular evidente, porém as células tratadas com TKI-258 nas concentrações estudadas, apresentaram morfologia arredondada, citoplasma escasso, filamentos de actina desorganizados e córtex celular preservado. O tratamento com TKI-258 (1 μM, 5 μM e 10 μM) inibiu a migração celular de maneira concentraçãodependente (ANOVA, F=97,749, df=3, 10; p<0,0001). O número de células tratadas com TKI-258 (5 μM) que invadiram a membrana recoberta com MatrigelTM foi significativamente menor que das células controle (t=6.708; df=5; P<0,001). Os resultados obtidos demonstraram que o inibidor tirosina quinase TKI-258 exerce um efeito inibitório sobre o citoesqueleto de actina, migração e invasão celular e provavelmente estes processos são regulados pelas via de sinalização: FGFRs e/ou do PDGFRs e/ou VEGFRs.Oral squamous cell carcinoma is extremely invasive, this behavior is regulated by binding of extracellular molecules to the cell membrane receptors. Currently, the blocking of these receptors with specific inhibitors is a new treatment modality of cancer. The TKI-258 inhibited phosphorylation of FGFRs VEGFRs and PDGFRs. Our aim was to analyze the effect of TKI-258 treatment on cell movement by using SCC-4 cell line from human oral squamous cell carcinoma. F-actin was stained with rhodamine conjugated to phalloidin and confocal analysis was performed. The migration and invasion (membrane covered with MatrigelTM) three-dimensional assays were performed, control and cells treated with TKI-258 that migrated through the membrane were counted after 24 hours. Control cells presented abundant cytoplasm with F-actin wide distributed and evident cell cortex, however cells treated with TKI258 at the concentrations studied showed round morphology, scanty cytoplasm, F-actin desorganized and preserved cell cortex. TKI-258 (1 μM, 5 μM and 10 μM) treatment inhibit migrating cells (ANOVA, F=97,749, df=3, 10; p<0.0001) and it was concentration dependent. Invading cell treated with 5 μM TKI-258 was significantly lower (t=6.708, df=5, p<0.001). These results suggest that the tyrosine kinase inhibitor TKI-258 has an inhibitory effect on F-actin, cell migration and cell invasion, probably these processes are regulated by FGFRs and/or PDGFRs and/or VEGFRs signaling pathways.Fundação de Amparo à Pesquisa do Estado de Minas GeraisCoordenação de Aperfeiçoamento de Pessoal de Nível SuperiorUniversidade Federal do Triângulo MineiroUniversidade Federal do Triângulo MineiroInstituto de Ciências da Saúde - ICS::Programa de Pós-Graduação em Ciências da SaúdeBrasilUFTMPrograma de Pós-Graduação em Ciências da SaúdeCREMA, Virgínia Oliveira66127211620http://lattes.cnpq.br/2599388555203811CARNEIRO, Anna Cecília Dias Maciel2019-07-16T14:23:17Z2016-07-20info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfCARNEIRO, Anna Cecília Dias Maciel. Efeito do TKI-258 sobre a motilidade de células de carcinoma epidermoide oral in vitro. 2016. 81f. 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dc.title.none.fl_str_mv Efeito do TKI-258 sobre a motilidade de células de carcinoma epidermoide oral in vitro
title Efeito do TKI-258 sobre a motilidade de células de carcinoma epidermoide oral in vitro
spellingShingle Efeito do TKI-258 sobre a motilidade de células de carcinoma epidermoide oral in vitro
CARNEIRO, Anna Cecília Dias Maciel
Invasão celular.
Migração celular.
Movimento celular.
Carcinoma de células escamosas.
TKI-258.
Inibidor tirosina quinase.
Cell invasion.
Cell migration.
Cell movement.
Squamous cell carcinoma.
TKI-258.
Tyrosine kinase inhibitor.
Morfologia
title_short Efeito do TKI-258 sobre a motilidade de células de carcinoma epidermoide oral in vitro
title_full Efeito do TKI-258 sobre a motilidade de células de carcinoma epidermoide oral in vitro
title_fullStr Efeito do TKI-258 sobre a motilidade de células de carcinoma epidermoide oral in vitro
title_full_unstemmed Efeito do TKI-258 sobre a motilidade de células de carcinoma epidermoide oral in vitro
title_sort Efeito do TKI-258 sobre a motilidade de células de carcinoma epidermoide oral in vitro
author CARNEIRO, Anna Cecília Dias Maciel
author_facet CARNEIRO, Anna Cecília Dias Maciel
author_role author
dc.contributor.none.fl_str_mv CREMA, Virgínia Oliveira
66127211620
http://lattes.cnpq.br/2599388555203811
dc.contributor.author.fl_str_mv CARNEIRO, Anna Cecília Dias Maciel
dc.subject.por.fl_str_mv Invasão celular.
Migração celular.
Movimento celular.
Carcinoma de células escamosas.
TKI-258.
Inibidor tirosina quinase.
Cell invasion.
Cell migration.
Cell movement.
Squamous cell carcinoma.
TKI-258.
Tyrosine kinase inhibitor.
Morfologia
topic Invasão celular.
Migração celular.
Movimento celular.
Carcinoma de células escamosas.
TKI-258.
Inibidor tirosina quinase.
Cell invasion.
Cell migration.
Cell movement.
Squamous cell carcinoma.
TKI-258.
Tyrosine kinase inhibitor.
Morfologia
description O carcinoma epidermoide oral é extremamente invasivo e este comportamento é regulado pela ligação de moléculas extracelulares aos receptores da membrana celular. Atualmente o bloqueio desses receptores com inibidores específicos constitui uma nova modalidade de tratamento para neoplasias. O TKI-258 inibe a autofosforilação dos receptores tirosina quinase: FGFRs, VEGFRs e PDGFRs. Este estudo visou avaliar o efeito do tratamento com TKI-258 sobre o movimento celular, utilizando a linhagem SCC-4 de carcinoma epidermoide oral humano. A F-actina foi evidenciada com rodamina conjugada à faloidina e os resultados foram analisados em microscopia confocal. Foram realizados ensaios tridimensionais de migração e invasão celular e as células controle e tratadas com TKI-258 foram contadas após 24 horas. As células controle apresentaram citoplasma abundante com ampla distribuição de F-actina e córtex celular evidente, porém as células tratadas com TKI-258 nas concentrações estudadas, apresentaram morfologia arredondada, citoplasma escasso, filamentos de actina desorganizados e córtex celular preservado. O tratamento com TKI-258 (1 μM, 5 μM e 10 μM) inibiu a migração celular de maneira concentraçãodependente (ANOVA, F=97,749, df=3, 10; p<0,0001). O número de células tratadas com TKI-258 (5 μM) que invadiram a membrana recoberta com MatrigelTM foi significativamente menor que das células controle (t=6.708; df=5; P<0,001). Os resultados obtidos demonstraram que o inibidor tirosina quinase TKI-258 exerce um efeito inibitório sobre o citoesqueleto de actina, migração e invasão celular e provavelmente estes processos são regulados pelas via de sinalização: FGFRs e/ou do PDGFRs e/ou VEGFRs.
publishDate 2016
dc.date.none.fl_str_mv 2016-07-20
2019-07-16T14:23:17Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv CARNEIRO, Anna Cecília Dias Maciel. Efeito do TKI-258 sobre a motilidade de células de carcinoma epidermoide oral in vitro. 2016. 81f. Dissertação (Mestrado em Ciências da Saúde) - Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Triângulo Mineiro, Uberaba, 2016.
http://bdtd.uftm.edu.br/handle/tede/771
identifier_str_mv CARNEIRO, Anna Cecília Dias Maciel. Efeito do TKI-258 sobre a motilidade de células de carcinoma epidermoide oral in vitro. 2016. 81f. Dissertação (Mestrado em Ciências da Saúde) - Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Triângulo Mineiro, Uberaba, 2016.
url http://bdtd.uftm.edu.br/handle/tede/771
dc.language.iso.fl_str_mv por
language por
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Instituto de Ciências da Saúde - ICS::Programa de Pós-Graduação em Ciências da Saúde
Brasil
UFTM
Programa de Pós-Graduação em Ciências da Saúde
publisher.none.fl_str_mv Universidade Federal do Triângulo Mineiro
Instituto de Ciências da Saúde - ICS::Programa de Pós-Graduação em Ciências da Saúde
Brasil
UFTM
Programa de Pós-Graduação em Ciências da Saúde
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