Avaliação do inibidor da p38/MAPK, ML3403 na proliferação celular de linhagens de glioma humano

• Ano de defesa: 2016
• Autor(a) principal: Tort, Ana Helena Bretanha Lopes
• Orientador(a): Morrone, Fernanda Bueno
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul
• Programa de Pós-Graduação: Programa de Pós-Graduação em Biotecnologia Farmacêutica
• Departamento: Faculdade de Farmácia
• País: Brasil
• Palavras-chave em Português: INIBIDORES DE PROTEÍNAS QUINASES; ENZIMAS - FARMACOLOGIA; GLIOMAS; ANGIOGÊNESE; BIOTECNOLOGIA - FÁRMACOS; FARMÁCIA
• Área do conhecimento CNPq: CIENCIAS DA SAUDE::FARMACIA
• Link de acesso: http://tede2.pucrs.br/tede2/handle/tede/6794

Gliomas are primary tumors of the central nervous system that are associated with a high mortality rate; they course with an average survival rate of 2 years after the diagnosis. Less than 5 % of glioma patients survive more than five years after diagnosis, even those treated with state of the art protocols, which include surgery, radiotherapy and chemotherapy. Tumors result from impairments of intracellular signaling pathways, including the p38/MAPK pathway, which, are responsible to control of cell proliferation and tumorigenesis, among other cellular responses. The goal of the present work was to investigate the effects of ML3403, an inhibitor of p38/MAPK, on the viability and proliferation of glioma cells, and to assess its effect when combined with bevacizumab (BVZ). BVZ already used in the clinical setting as anadjuvant for treating gliomas. It is a monoclonal antibody against VEGF-A receptor and thus reduces the signaling involved in tumor angiogenesis. U138 and U251 glioma cells were treated with ML3403 (0.1 to 200 μM) and BVZ (1 to 200 μg/mL) and later assessedfor cell viability, by MTT method and proliferation by cell counting. The results demonstrate that treatment with ML3403 reduces glioma cell viability and proliferation. Co-treatment with BVZ does not present any significant effect. The use of p38/MAPK inhibitors may constitute an interesting treatment against glioma progression.