Analysis of the effect of cyclooxygenase on the expression and activity of Multiple Drug Resistance Proteins (MDRP) in human glioma.

O glioblastoma multiforme, tumor de alta malignidade é conhecido por ser um câncer de difícil cura devido sua resistência ao tratamento de quimioterapia. Neste contexto sabe-se a existência de um gene responsável pelo fenótipo de resistência (MDR) e produção de proteínas associadas à resistência a uma grande variedade de drogas (MRPs). As proteínas de resistência a múltiplas drogas funcionam como bombas de efluxo, capazes de retirar das células compostos citotóxicos, deixando o tratamento quimioterápico sem o efeito esperado. Atualmente a suposta relação entre as ciclooxigenases e as proteínas de resistência a múltiplas drogas tem sido estudada em alguns tipos de câncer e na maioria deles observa-se uma relação positiva no sentido da COX poder participar da super-expressão de proteínas de resistência, fazendo com que as células fiquem ainda mais resistentes ao tratamento. O objetivo do projeto é analisar o possível efeito das COX 1 e 2 na expressão e atividade de MDRs e MRPs.Glioblastoma multiforme, a highly malignant tumor is difficult to cure because of its resistance to chemotherapy treatment. A well-established cause of multidrug resistance (MDR) involves the increased expression of members of the ATP binding cassette (ABC) transporter superfamily, many of which transport chemotherapeutic compounds from cells. Multidrug resistance proteins can act as efflux pumps allowing. The cells to remove cytotoxic compounds and often leaving the chemotherapy treatment without the expected effect. The possible relationship between cyclooxygenase and MDRPs has been studied in several cancers and in most there is a positive relationship. The role of cyclooxygenases (COX) has been extensively studied, especially COX-2, which is expressed in many human cancers. Recently studies have been performed to identify whether the presence of COXs has some involvement with the expression of MDRPs. A positive correlation between COXs and MDRPs has been identified in certain cancers. To analyze the possible relationship between COX 1 and 2 and the expression and activity of MDRs and MRPs in gliomas. The following family members of ABC transporters were studied: MDR1, MRP1, MRP2, MRP3, MRP4 e MRP5. Our analysis show e da constitutive expression of Cox-2 in U138MG and U251 cells, as well as the expression of all the MDRPs studied (MDR1 and MRPs1-6). However, in the U138MG cell line where COX-1 was not is expressed there was a large decrease in the expression of MDR1 in comparison with the COX 1 positive U251 cell line