ABSTRACT
AIMS: The objective of this study was to analyze the influence of obesity and insulin resistance on tumor development and, in turn, the effect of insulin sensitizing agents. MAIN METHODS: Male offspring of Wistar rats received monosodium glutamate (400mg/kg) (obese) or saline (control) from the second to sixth day after birth. Sixteen-week-old control and obese rats received 5×10(5) Walker-256 tumor cells, subcutaneously injected into the right flank. Some of the obese and control rats received concomitant treatment with metformin (300mg/kg) by gavage. At the 18th week, obesity was characterized. The percentage of rats that developed tumors, the tumor relative weight and the percentage of cachexia incidence were analyzed. The tumor tissue was evaluated histologically by means of hematoxylin and eosin staining. KEY FINDINGS: Metformin did not correct the insulin resistance in obese rats. The tumor development was significantly higher in the obese group, whereas metformin treatment reduced it. After pathological analysis, we observed that the tumor tissues were similar in all groups except for adipocytes, which were found in greater quantity in the obese and metformin-treated obese groups. The area of tumor necrosis was higher in the group treated with metformin when compared with the untreated one. SIGNIFICANCE: Metformin reduced Walker-256 tumor development but not cachexia in obese rats. The reduction occurred independently of the correction of insulin resistance. Metformin increased the area of necrosis in tumor tissues, which may have contributed to the reduced tumor development.
Subject(s)
Carcinoma 256, Walker/pathology , Carcinoma 256, Walker/prevention & control , Metformin/therapeutic use , Obesity/drug therapy , Obesity/pathology , Animals , Carcinoma 256, Walker/etiology , Male , Necrosis/etiology , Necrosis/pathology , Necrosis/prevention & control , Obesity/complications , Random Allocation , Rats , Rats, Wistar , Xenograft Model Antitumor Assays/methodsSubject(s)
Linoleic Acid/metabolism , Animals , Carcinoma 256, Walker/etiology , Carcinoma 256, Walker/metabolism , Carcinoma 256, Walker/prevention & control , Cell Communication , Dietary Fats/administration & dosage , Epoprostenol/metabolism , Humans , Hydroxyeicosatetraenoic Acids/metabolism , Hydroxyeicosatetraenoic Acids/pharmacology , Inflammation/metabolism , Inflammation/prevention & control , Linoleic Acids/metabolism , Linoleic Acids/pharmacology , Neoplasm Metastasis , Rats , Rats, Wistar , Thrombosis/metabolism , Thrombosis/prevention & controlABSTRACT
The results of studies conducted on 355 white nonpedigree male rats (268 experimental and 87 intact animals) indicated that nephrogenic hypertension: a) potentiates the development of benz(a) pyrene induced blastomas; b) enhances, as a rule, the growth of transplantable tumors: carcinoma RS-1 and sarcoma 45; c) results in a tendency to more frequent metastasization of the tumors (Walker carcinosarcoma and Zajdela ascites hepatoma).
