Efeitos dos ácidos graxos ômega-3 na progressão do câncer de próstata
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Data
2020-03-05
Autores
Amaro, Gustavo Matheus
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O câncer de próstata (CaP) é um dos tipos mais recorrentes de câncer em homens e o consumo excessivo de lipídeos saturados favorece o seu desenvolvimento. Ao contrário, dietas ricas em ácidos graxos poli-insaturados (PUFA) tipo ômega-3 (n-3) tem sido associadas com menor incidência do CaP. O presente trabalho avaliou as repercussões do consumo de ácidos graxos PUFAs n-3 da série marinha, ácido docosahexaenoico (DHA) e ácido eicosapentaenoico (EPA), sobre a progressão tumoral na próstata ventral de camundongos transgênicos para o adenocarcinoma de próstata (TRAMP). Camundongos TRAMP foram alimentados com dieta padrão e eutanasiados com 8 (C8), 12 (C12) e 20 (C20) semanas de vida ou então alimentados com uma dieta rica em óleo de peixe (10% óleo de peixe) a partir da oitava semana de vida e então eutanasiados com 12 (T12) ou 20 semanas (T20). Os resultados adquiridos demonstraram o aumento na proliferação celular bem como na expressão tecidual do receptor de andrógeno (AR) e glicocorticoide (GR) e no número de linfócitos T na próstata dos grupos controles conforme o aumento da idade e da agressividade das lesões. A intervenção dietética com PUFAs n-3 proporcionou a preservação do microambiente glandular levando a uma menor frequência de lesões proliferativas, indicando um atraso na progressão tumoral, onde foi observado níveis de proliferação celular, da expressão tecidual de AR e GR e de linfócitos T inferiores que seus controles de mesma idade. Ainda, o consumo de DHA/EPA promoveu uma melhora no perfil metabólico dos animais que apresentaram uma redução nos níveis de triglicerídeos e colesterol. Assim, concluímos que a incorporação de DHA/EPA na dieta é capaz de reduzir a severidade da doença, levando ao atraso da progressão tumoral, destacando que a intervenção dietética é um mecanismo eficaz de modular a progressão tumoral, podendo ser utilizada em novas abordagens terapêuticas para o CaP.
Prostate cancer (PCa) is one of the most frequent cancers among male individual and saturated lipid intake is linked to its development. However, diets rich in omega-3 (n-3) polyunsaturated fatty acid (PUFA) have been associated to lower PCa development risk. The present study assessed the outcome of the marine n-3 PUFA intake, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), upon tumor progression at the transgenic adenocarcinoma of the mouse prostate (TRAMP). TRAMP mice were chow-fed and euthanized at 8 (C8), 12 (C12) and 20th (C20) week of age or fed with a fish oil-enriched diet from 8 to 12 (T12) or 20th (T20) week of age and then euthanized. The results indicated an increase in proliferation rate, tissue expression of androgen receptor (AR) and glucocorticoid receptor (GR) and the number of T-cells at the prostate of the control groups according to the increase of age and aggressiveness of the lesions. Dietary intervention with n-3 PUFA led to the maintenance of the glandular microenvironment, highlighted by a reduction of the frequency of proliferative lesions, indicating a delay in PCa progression whereas the levels of cell proliferation, tissue expression of AR and GR and the number of T-cells were lower than the control groups of the same age. Also, DHA/EPA intake promoted a lowering effect of serum triglycerides and cholesterol, improving the metabolic profile of these animals. Thereby incorporation o DHA/EPA on diet is capable of decrease the severity of PCa by delaying the disease progression, highlighting that dietary interventions are effective mechanisms to modulate tumor progression and may be used in new therapeutic approaches in PCa.
Prostate cancer (PCa) is one of the most frequent cancers among male individual and saturated lipid intake is linked to its development. However, diets rich in omega-3 (n-3) polyunsaturated fatty acid (PUFA) have been associated to lower PCa development risk. The present study assessed the outcome of the marine n-3 PUFA intake, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), upon tumor progression at the transgenic adenocarcinoma of the mouse prostate (TRAMP). TRAMP mice were chow-fed and euthanized at 8 (C8), 12 (C12) and 20th (C20) week of age or fed with a fish oil-enriched diet from 8 to 12 (T12) or 20th (T20) week of age and then euthanized. The results indicated an increase in proliferation rate, tissue expression of androgen receptor (AR) and glucocorticoid receptor (GR) and the number of T-cells at the prostate of the control groups according to the increase of age and aggressiveness of the lesions. Dietary intervention with n-3 PUFA led to the maintenance of the glandular microenvironment, highlighted by a reduction of the frequency of proliferative lesions, indicating a delay in PCa progression whereas the levels of cell proliferation, tissue expression of AR and GR and the number of T-cells were lower than the control groups of the same age. Also, DHA/EPA intake promoted a lowering effect of serum triglycerides and cholesterol, improving the metabolic profile of these animals. Thereby incorporation o DHA/EPA on diet is capable of decrease the severity of PCa by delaying the disease progression, highlighting that dietary interventions are effective mechanisms to modulate tumor progression and may be used in new therapeutic approaches in PCa.
Descrição
Palavras-chave
Câncer de próstata, Dieta, Ácidos graxos ômega-3, Receptores nucleares, Prostate cancer, Diet, Omega-3 fatty acids, Nuclear receptors