Efeito do TKI-258 sobre a proliferação celular em carcinoma epidermoide oral in vitro
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| Data de Publicação: | 2018 |
| 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/752 |
Resumo: | O carcinoma epidermoide oral apresenta altas taxas de mortalidade. Os receptores tirosina quinase, FGFRs, PDGFRs e VEGFRs, estão amplificados e/ou superexpressos nessa neoplasia e são bloqueados pelo inibidor TKI-258. Esses receptores ativam a PI3K, proteína intracelular que está frequentemente associada à carcinogênese, que pode ser bloqueada pelos inibidores LY294002 e Wortmannin. O objetivo deste estudo foi avaliar o efeito do tratamento com TKI-258 sobre a proliferação celular, e o papel da proteína PI3K nas vias de sinalização inibidas por esse inibidor em carcinoma epidermoide oral in vitro. Através dos ensaios de incorporação do BrdU e imunoexpressão do KI-67, marcadores de proliferação celular, foi determinada a taxa de proliferação de células SCC-4 de carcinoma epidermoide oral controle e tratadas por 6 h com: TKI-258 1 µM, 5 µM e 10 µM; LY294002 60 µM e/ou Wortmannin 2 µM; TKI 5 μM somente ou associado ao LY294002 ou ao Wortmannin; e, TKI 5 μM combinado com LY294002 e Wortmannin. Foi considerada uma significância de p<0,05. O tratamento com TKI-258 reduziu a taxa de proliferação de células SCC-4 que incorporaram BrdU [F(3,11) = 120,807, p<0,0001] e imunoexpressaram KI-67 [F(3,11) = 222,379, p<0,0001]. O percentual de células proliferativas também foi menor após o tratamento com os inibidores da PI3K, LY294002 e/ou Wortmannin, incorporação do BrdU [F(3,11) = 477,578, p<0,0001] e imunoexpressão do KI-67 [F(3,11) = 421,762, p<0,0001]. A associação do TKI-258 5 µM com LY294002 e/ou Wortmannin diminuiu ainda mais a taxa de proliferação na incorporação do BrdU [F(3,11) = 252,324, p<0,0001] e imunoexpressão do KI-67 [F(3,11) = 295,346, p<0,0001]. Os resultados obtidos neste estudo demonstraram que o TKI-258 apresenta um efeito antiproliferativo em células SCC-4 de carcinoma epidermoide oral e esse processo possivelmente pode ser regulado pelos receptores tirosina quinase bloqueados por esse inibidor, por meio de vias dependentes e independentes de PI3K. |
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Efeito do TKI-258 sobre a proliferação celular em carcinoma epidermoide oral in vitroCarcinoma epidermoide oral.Inibidores tirosina quinase.PI3K.Proliferação celular.Cell proliferation.Oral squamous cell carcinoma.PI3K.Tyrosine kinase inhibitors.MorfologiaO carcinoma epidermoide oral apresenta altas taxas de mortalidade. Os receptores tirosina quinase, FGFRs, PDGFRs e VEGFRs, estão amplificados e/ou superexpressos nessa neoplasia e são bloqueados pelo inibidor TKI-258. Esses receptores ativam a PI3K, proteína intracelular que está frequentemente associada à carcinogênese, que pode ser bloqueada pelos inibidores LY294002 e Wortmannin. O objetivo deste estudo foi avaliar o efeito do tratamento com TKI-258 sobre a proliferação celular, e o papel da proteína PI3K nas vias de sinalização inibidas por esse inibidor em carcinoma epidermoide oral in vitro. Através dos ensaios de incorporação do BrdU e imunoexpressão do KI-67, marcadores de proliferação celular, foi determinada a taxa de proliferação de células SCC-4 de carcinoma epidermoide oral controle e tratadas por 6 h com: TKI-258 1 µM, 5 µM e 10 µM; LY294002 60 µM e/ou Wortmannin 2 µM; TKI 5 μM somente ou associado ao LY294002 ou ao Wortmannin; e, TKI 5 μM combinado com LY294002 e Wortmannin. Foi considerada uma significância de p<0,05. O tratamento com TKI-258 reduziu a taxa de proliferação de células SCC-4 que incorporaram BrdU [F(3,11) = 120,807, p<0,0001] e imunoexpressaram KI-67 [F(3,11) = 222,379, p<0,0001]. O percentual de células proliferativas também foi menor após o tratamento com os inibidores da PI3K, LY294002 e/ou Wortmannin, incorporação do BrdU [F(3,11) = 477,578, p<0,0001] e imunoexpressão do KI-67 [F(3,11) = 421,762, p<0,0001]. A associação do TKI-258 5 µM com LY294002 e/ou Wortmannin diminuiu ainda mais a taxa de proliferação na incorporação do BrdU [F(3,11) = 252,324, p<0,0001] e imunoexpressão do KI-67 [F(3,11) = 295,346, p<0,0001]. Os resultados obtidos neste estudo demonstraram que o TKI-258 apresenta um efeito antiproliferativo em células SCC-4 de carcinoma epidermoide oral e esse processo possivelmente pode ser regulado pelos receptores tirosina quinase bloqueados por esse inibidor, por meio de vias dependentes e independentes de PI3K.Oral squamous cell carcinoma presents high mortality rates. Tyrosine kinase receptors, FGFRs, PDGFRs and, VEGFRs, are amplified and/or overexpressed in this neoplasm and are blocked by the inhibitor TKI-258. These receptors activate PI3K, an intracellular protein that is often associated with carcinogenesis, that can be blocked by inhibitors LY294002 and Wortmannin. The aim of this study was to evaluate the effect of TKI-258 treatment on cell proliferation, and the role of PI3K protein in signaling pathways inhibited by this inhibitor in oral squamous cell carcinoma in vitro. Through the BrdU incorporation assays and KI-67 immunoexpression, cell proliferation markers, SCC-4 cells of oral squamous cell carcinoma were quantified and treated for 6 h with TKI-258 (1, 5 and 10 μM); LY294002 60 μM (LY) and/or Wortmannin 2 μM (WTN); TKI-258 5 μM only or associated with LY or WTN; and, 5 μM TKI-258 combined with LY and WTN. A significance of p<0.05 was considered. Treatment with TKI-258 reduced the proliferation rate in SCC-4 cells incorporated BrdU [F(3,11) =120.807, p<0.0001] and immunoexpressed KI-67 [F(3,11) = 222.379, p<0.0001]. The reduction percentage was also lower after treatment with PI3K, LY and/or WTN inhibitors, incorporation of BrdU [F(3,11) = 477.578, p<0.0001] and KI-67 [F(3,11) = 421.762, p<0.0001]. And, the association of 5 μM TKI-258 with LY and/or WTN further decreased the proliferation rate in BrdU incorporation [F(3.11) = 252.324, p<0.0001] and KI-67 immunoexpression [F(3,11) = 295.346, p<0.0001]. The results obtained in this study demonstrated that TKI-258 exhibits an antiproliferative effect on SCC-4 cells of OSCC and this process may possibly be regulated by the tyrosine kinase receptors blocked by that inhibitor, by means of PI3K dependent and independent pathways.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFundação de Amparo à Pesquisa do Estado de Minas GeraisUniversidade 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/2599388555203811SILVEIRA, Isadora Caixeta da2019-07-10T13:43:06Z2018-11-13info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfSILVEIRA, Isadora Caixeta da. Efeito do TKI-258 sobre a proliferação celular em carcinoma epidermoide oral in vitro. 2018. 72f. 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Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/21042768 >.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFTMinstname:Universidade Federal do Triangulo Mineiro (UFTM)instacron:UFTM2019-07-11T04:00:33Zoai:bdtd.uftm.edu.br:tede/752Biblioteca Digital de Teses e Dissertaçõeshttp://bdtd.uftm.edu.br/PUBhttp://bdtd.uftm.edu.br/oai/requestbdtd@uftm.edu.br||bdtd@uftm.edu.bropendoar:2019-07-11T04:00:33Biblioteca Digital de Teses e Dissertações da UFTM - Universidade Federal do Triangulo Mineiro (UFTM)false |
| dc.title.none.fl_str_mv |
Efeito do TKI-258 sobre a proliferação celular em carcinoma epidermoide oral in vitro |
| title |
Efeito do TKI-258 sobre a proliferação celular em carcinoma epidermoide oral in vitro |
| spellingShingle |
Efeito do TKI-258 sobre a proliferação celular em carcinoma epidermoide oral in vitro SILVEIRA, Isadora Caixeta da Carcinoma epidermoide oral. Inibidores tirosina quinase. PI3K. Proliferação celular. Cell proliferation. Oral squamous cell carcinoma. PI3K. Tyrosine kinase inhibitors. Morfologia |
| title_short |
Efeito do TKI-258 sobre a proliferação celular em carcinoma epidermoide oral in vitro |
| title_full |
Efeito do TKI-258 sobre a proliferação celular em carcinoma epidermoide oral in vitro |
| title_fullStr |
Efeito do TKI-258 sobre a proliferação celular em carcinoma epidermoide oral in vitro |
| title_full_unstemmed |
Efeito do TKI-258 sobre a proliferação celular em carcinoma epidermoide oral in vitro |
| title_sort |
Efeito do TKI-258 sobre a proliferação celular em carcinoma epidermoide oral in vitro |
| author |
SILVEIRA, Isadora Caixeta da |
| author_facet |
SILVEIRA, Isadora Caixeta da |
| author_role |
author |
| dc.contributor.none.fl_str_mv |
CREMA, Virgínia Oliveira 66127211620 http://lattes.cnpq.br/2599388555203811 |
| dc.contributor.author.fl_str_mv |
SILVEIRA, Isadora Caixeta da |
| dc.subject.por.fl_str_mv |
Carcinoma epidermoide oral. Inibidores tirosina quinase. PI3K. Proliferação celular. Cell proliferation. Oral squamous cell carcinoma. PI3K. Tyrosine kinase inhibitors. Morfologia |
| topic |
Carcinoma epidermoide oral. Inibidores tirosina quinase. PI3K. Proliferação celular. Cell proliferation. Oral squamous cell carcinoma. PI3K. Tyrosine kinase inhibitors. Morfologia |
| description |
O carcinoma epidermoide oral apresenta altas taxas de mortalidade. Os receptores tirosina quinase, FGFRs, PDGFRs e VEGFRs, estão amplificados e/ou superexpressos nessa neoplasia e são bloqueados pelo inibidor TKI-258. Esses receptores ativam a PI3K, proteína intracelular que está frequentemente associada à carcinogênese, que pode ser bloqueada pelos inibidores LY294002 e Wortmannin. O objetivo deste estudo foi avaliar o efeito do tratamento com TKI-258 sobre a proliferação celular, e o papel da proteína PI3K nas vias de sinalização inibidas por esse inibidor em carcinoma epidermoide oral in vitro. Através dos ensaios de incorporação do BrdU e imunoexpressão do KI-67, marcadores de proliferação celular, foi determinada a taxa de proliferação de células SCC-4 de carcinoma epidermoide oral controle e tratadas por 6 h com: TKI-258 1 µM, 5 µM e 10 µM; LY294002 60 µM e/ou Wortmannin 2 µM; TKI 5 μM somente ou associado ao LY294002 ou ao Wortmannin; e, TKI 5 μM combinado com LY294002 e Wortmannin. Foi considerada uma significância de p<0,05. O tratamento com TKI-258 reduziu a taxa de proliferação de células SCC-4 que incorporaram BrdU [F(3,11) = 120,807, p<0,0001] e imunoexpressaram KI-67 [F(3,11) = 222,379, p<0,0001]. O percentual de células proliferativas também foi menor após o tratamento com os inibidores da PI3K, LY294002 e/ou Wortmannin, incorporação do BrdU [F(3,11) = 477,578, p<0,0001] e imunoexpressão do KI-67 [F(3,11) = 421,762, p<0,0001]. A associação do TKI-258 5 µM com LY294002 e/ou Wortmannin diminuiu ainda mais a taxa de proliferação na incorporação do BrdU [F(3,11) = 252,324, p<0,0001] e imunoexpressão do KI-67 [F(3,11) = 295,346, p<0,0001]. Os resultados obtidos neste estudo demonstraram que o TKI-258 apresenta um efeito antiproliferativo em células SCC-4 de carcinoma epidermoide oral e esse processo possivelmente pode ser regulado pelos receptores tirosina quinase bloqueados por esse inibidor, por meio de vias dependentes e independentes de PI3K. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018-11-13 2019-07-10T13:43:06Z |
| 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 |
SILVEIRA, Isadora Caixeta da. Efeito do TKI-258 sobre a proliferação celular em carcinoma epidermoide oral in vitro. 2018. 72f. Dissertação (Mestrado em Ciências da Saúde) - Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Triângulo Mineiro, Uberaba, 2018. http://bdtd.uftm.edu.br/handle/tede/752 |
| identifier_str_mv |
SILVEIRA, Isadora Caixeta da. Efeito do TKI-258 sobre a proliferação celular em carcinoma epidermoide oral in vitro. 2018. 72f. Dissertação (Mestrado em Ciências da Saúde) - Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Triângulo Mineiro, Uberaba, 2018. |
| url |
http://bdtd.uftm.edu.br/handle/tede/752 |
| dc.language.iso.fl_str_mv |
por |
| language |
por |
| dc.relation.none.fl_str_mv |
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