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Previous issue date: 2015-03-09 / Glioblastoma multiform (GBM) is a highly aggressive tumor of the central nervous system and has a few available therapies. In GBM, proinflammatory signaling pathways, such as STAT3 and NF- ?B are aberrantly activated and associated with cell proliferation, survival, invasion and resistance to chemotherapy. Therefore, inhibition of these pro-inflammatory pathways has been suggested as a strategy to combat malignant cells. Resolvins of D-series promote resolution of inflammation by decreasing the activation of NF-?B. The Resolvin D2 (RvD2) is derived from a double sequence of docosahexaenoic acid lipoxygenation, which is derived from the essential fatty acid Omega-3. Our hypothesis is that the resolvins, by direct or indirect inhibition of pro-inflammatory pathways, could compromise the survival and growth of glioma. Our goal is to assess the role of RvD2 and its precursor 17 (R) HDHA (HR17) on tumor cell proliferation and survival in murine glioma model. For this, murine glioma cell line (GL261) was treated in vitro with RvD2 and HR17, and cell death and proliferation were evaluated. Furthermore, the effect of RvD2 and HR17 was evaluated in vivo after GL261 brain implantation; histopathological characteristics and immunohistochemistry for activated caspase-3 were evaluated to. It was found that RvD2 GL261 induces apoptosis in vitro. Furthermore, in vivo treatment of RvD2 and HR17 increased the number of tumor cells positive for activated caspase-3, although not alter tumor area. Interestingly, the HR17 treatment reduces tumor mitotic index in vivo. These results suggest that RvD2 and HR17 have a potential role in the induction of apoptosis in murine glioma cells. / Glioblastoma multiforme (GBM) ? um tumor altamente agressivo do Sistema Nervoso Central e possui poucas terapias dispon?veis. Em GBM, vias de sinaliza??o pr?-inflamat?rias, como da STAT3 e NF-?B, s?o aberrantemente ativadas e associadas com a prolifera??o celular, sobreviv?ncia, invas?o e resist?ncia ? quimioterapia. Por conseguinte, a inibi??o dessas vias pr?inflamat?rias tem sido sugerida como uma estrat?gia para combater as c?lulas malignas. As resolvinas da s?rie D promovem resolu??o da inflama??o diminuindo a ativa??o de NF-?B. A Resolvina D2 (RvD2) deriva de uma sequencia de dupla lipoxigena??o do ?cido docosahexaen?ico, o qual ? derivado do ?cido graxo essencial Omega-3. Nossa hip?tese ? que as resolvinas, por inibi??o direta ou indireta de vias pr?-inflamat?rias, poderiam comprometer a sobreviv?ncia e o crescimento do glioma. Nosso objetivo consiste em avaliar o papel da RvD2 e de seu precursor 17(R)HDHA (HR17) sobre a prolifera??o de c?lulas tumorais e sobreviv?ncia em um modelo de glioma murino. Para isso, a linhagem de c?lulas de glioma murino (GL261) foi tratada in vitro com RvD2 e HR17, e amorte celular e prolifera??o foram avaliadas. Al?m disso, o efeito de RvD2 e HR17 foi avaliado in vivo ap?s o implante de GL261 no c?rebro, avaliando-se caracter?sticas histopatol?gicas e a imunohistoqu?mica para caspase-3 ativada. Verificou-se que RvD2 induz apoptose de GL261 in vitro. Al?m disso, o tratamento de RvD2 e HR17 in vivo aumentou o n?mero de c?lulas tumorais positivas para caspase-3 ativada, embora n?o alterassem a ?rea do tumor. Curiosamente, o tratamento HR17 reduz o ?ndice mit?tico tumoral in vivo. Estes resultados sugerem que RvD2 e HR17 t?m um potencial papel na indu??o de apoptose em c?lulas de glioma murino.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/6174 |
| Date | 09 March 2015 |
| Creators | Corr?a, Laura Trevizan |
| Contributors | Souza, Ana Paula Duarte de |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Biotecnologia Farmac?utica, PUCRS, Brasil, Faculdade de Farm?cia |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2304961219518893267, 600, 600, 600, -8380654636843378116, 6997636413449754996 |
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