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Doctoral Thesis
DOI
10.11606/T.42.2013.tde-26092013-110519
Document
Author
Full name
Eveline Aparecida Isquierdo Fonseca
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Fortes, Zuleica Bruno (President)
Campa, Ana
Chammas, Roger
Colquhoun, Alison
Velloso, Lício Augusto
Title in Portuguese
Efeito da metformina sobre o desenvolvimento tumoral na obesidade: mecanismos envolvidos.
Keywords in Portuguese
Apoptose
Estresse oxidativo
Insulina
Metformina
Necrose
Obesidade
Abstract in Portuguese
A influência da obesidade induzida por glutamato monossódico em ratos sobre o desenvolvimento do tumor de Walker-256 e os efeitos da metformina (300mg/kg, v.o., 15 dias) foram investigados. Na 16ª semana de vida, inocularam-se as células tumorais e iniciou-se o tratamento. Após 15 dias, analisou-se o crescimento tumoral. A viabilidade de células tumorais, MCF-7, tratadas com meformina foi avaliada. A obesidade contribuiu para maior desenvolvimento tumoral e reduziu a sobrevida dos ratos. A metformina foi eficaz em impedir o aumento do tumor e aumentou a sobrevida dos ratos. Teve efeito antiproliferativo sobre as células MCF-7, efeito esse relacionado ao bloqueio do ciclo celular, estresse oxidativo, aumento na apoptose e necrose celulares, e aumento na atividade da AMPK e do FOXO3a. Conclui-se que a obesidade contribui de maneira significativa para o desenvolvimento tumoral e que a metformina é eficaz em diminuí-lo.
Title in English
Effect of metformin in the tumor development in obese: mecchanisms involved.
Keywords in English
Apoptosis
Insulin
Metformin
Necrosis
Obesity
Oxidative stress
Abstract in English
The influence of obesity induced by monossodium glutamate in rats on Walker-256 tumor development and the metformin (300/kg, b.w., 15 days) effect were analyzed. At the 16th week, 1x107 Walker-256 tumor cells were inoculated and the treatment with metformin was started. Following this treatment, the tumor growth was analyzed. The cell viability of MCF-7 cells treated with metformin was analyzed. Obesity positively contributed for tumor development and it reduced life span of the rats. Metformin reduced the tumor development and increased the life span of the rats. It presented an antiproliferative effect in MCF-7 cells. Effect associated with an increase in oxidative stress, apoptosis, necrosis and cell cycle arrest in G0-G1 phase. Furthermore, its effect is associated with an increased in AMPK and FOXO3a activities. In conclusion, obesity contributed significantly to tumor development and metformin is effective in reduced it.
 
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Publishing Date
2013-12-06
 
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