Influência da composição de lipídeos da dieta no desenvolvimento do carcinoma mamário murino 4T1

Abstract

Dietary lipids have been shown to influence breast cancer development at several stages in the carcinogenic process. Thus, the aim of this study was to investigate the effect oils,containing low n-6/n-3 ratio, in tumor development and metastatic dissemination of 4T1 murine mammary carcinoma. BALB/c mice were randomly divided into four groups of 14 animals each fed semisynthetic AIN-93G diet containing 4g/100g soybean oil (Control), canola oil (Canola), fish oil (Fish) or flaxseed oil (linseed). The animals were fed ad libitum for 50 days, and on the 30th day seven animals in each group were inoculated with 4T1 cells (2.5 x 106) and named: Control 4T1, Canola 4T1, Fish 4T1 and Flaxseed 4T1. Body weight was recorded weekly. Cholesterol and triglycerides were determined by enzymatic assay. Fractionation of serum lipoproteins was performed by Fast Protein Liquid Chromatografy system. Quantification of hepatic lipids and cecal was performed as described by Folch et al. Assessment of lipid peroxidation was based on the determination of concentration of thiobarbituric acid reactive substances (TBARS). For histological analysis of the primary tumor and metastases, samples were collected, fixed and intended for cutting and staining with hematoxylin & eosin, and for blades for immunohistochemistry to identify CDC47. Further biochemical analyzes for assessing inflammation were conducted by plasma levels of the enzymes N-acetyl-beta-D-glucosaminidase (NAG) and myeloperoxidase (MPO), angiogenic, through the levels of vascular endothelial growth factor (VEGF) and hemoglobin (Hb), and the participation of the cytokine TNF-. There was no change in body weight of the animals during the experimental period. The animals in the Control 4T1 group decreased adduced lipoprotein cholesterol and increased fecal excretion of total lipids, cholesterol and triglycerides compared to Control group. The Flaxseed 4T1 group had increased cholesterol and triglycerides circulating in relation to Linseed and Control 4T1 groups and decreased lipid content in the liver compared to Flaxseed group. Likewise, the Fish 4T1 group had higher levels of circulating triglycerides in relation to Fish group, but had lower triglyceride content in the liver compared to the other groups with tumor. Canola 4T1 group had lower hepatic levels of TBARS. No change in tumor growth and metastasis number among the groups. In relation to cell proliferation, Canola 4T1 group had higher expression of CDC47 protein compared to Control 4T1 group. The Fish 4T1 group showed increased MPO and NAG reduction in tumor site. No significant change was observed in the Hb concentration, however, increased by VEGF in Fish 4T1 group compared to other groups. Furthermore there was no change of TNF- in the tumor site. This present study that showed different oils did not alter tumor growth and the number of metastases, but exert distinct effects on lipid metabolism, inflammatory and angiogenic processes effects, and cellular proliferation in murine mammary carcinoma 4T1 model.