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Doctoral Thesis
DOI
10.11606/T.87.2011.tde-10022012-151003
Document
Author
Full name
Hamilton de Campos Zampolli
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Tavassi, Ana Marisa Chudzinski (President)
Dagli, Maria Lucia Zaidan
Folgueira, Maria Aparecida Azevedo Koike
Maria, Durvanei Augusto
Ortiz, Valdemar
Title in Portuguese
Avaliação dos efeitos antineoplásicos do Amblyomin-X em carcinoma de células renais.
Keywords in Portuguese
Antineoplásicos
Carcinoma
Células cultivadas de tumor
Citocinas
Microscopia eletrônica de varredura
Proliferação celular
Abstract in Portuguese
Introdução: O carcinoma de células renais metastático (CCRm) é um tumor altamente agressivo e resistente. Seu tratamento é baseado em terapia alvo molecular e citocinas. Avaliamos os efeitos antineoplásicos do Amblyomin-X, sobre CCR. Métodos: Avaliadas culturas de CCR RENCA e fibroblastos normais NIH/3T3 tratadas ou não com Amblyomin-X. Realizados ensaios de viabilidade celular por MTT e determinação, por citometria de fluxo, da proporção de células em apoptose/necrose; expressão da P-gp; Bad; Bax; Bcl-2; ciclina D1; caspase 3; Ki-67; p53; VEGFR1; citocromo c; análise das fase do ciclo celular; e atividade do proteassoma. Analisamos as populações celulares por microscopia eletrônica de varredura. Empregados testes T e One-way ANOVA para análise estatística. Resultados: O Amblyomin-X demonstrou citotoxicidade em células RENCA por indução de apoptose, diminuição de proliferação celular, inibição do proteassoma e modulação do ciclo celular em G0/G1. Em fibroblastos normais não houve citotoxicidade Conclusão: O Amblyomin-X apresentou efeito antineoplásico em CCR e não exerceu efeito citotóxico em células normais, demonstrando um possível potencial terapêutico no tratamento do CCRm. Estudos futuros deverão confirmar estes resultados.
Title in English
Evaluation of Amblyomin-X antineoplasic effects on renal cell carcinoma.
Keywords in English
Anticancer agents
Carcinoma
Cell proliferation
Cells cultured tumor
Cytokines
Scanning electron microscopy
Abstract in English
Introduction: Metastatic renal cell carcinoma (mRCC) is a highly agressive and resistant tumour. Its treatment is based on targeted therapies and cytokines. We have evaluated the antineoplasic effects of Amblyomin-X on RCC. Methods: RCC (RENCA) and fibroblasts (NIH/3T3) cell cultures treated or not with Amblyomin-X were evaluated. MTT assay was performed to determine cell viability. Apoptosis/necrosis ratio; expression of P-gp; Bad; Bax; Bcl-2; cyclin D1; caspase-3; Ki-67; p53; VEGFR1; cytochrome c; cell cycle analysis and proteasome activity were obtained by flow cytometry. Cellular populations were analised by Scanning Electron Microscopy. Statistical analyses was performed using T-Tests and One-way ANOVA. Results: Amblyomin-X showed cytotoxic activity on RENCA tumor cells. It has induced apoptosis, decreased tumor cell proliferation, targeted the ubiquitinproteasome system and modulated genes related to cell cycle in G0/G1. There was no toxicity on fibroblasts. Conclusion: Amblyomin-X showed antineoplasic effects on RCC cells preserved normal fibroblast cells. There is a potential role of its therapeutic use in mRCC treatment. Future studies should confirm our initial results.
 
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Publishing Date
2012-03-01
 
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