title: Metformin reduces the stimulatory effect of obesity on in vivo Walker-256 tumor development and increases the area of tumor necrosis.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Eveline Aparecida Isquierdo
authors: EA
authors: Fonseca
authors: Maria Aparecida
authors: MA
authors: de Oliveira
authors: Núbia de Souza
authors: Nde S
authors: Lobato
authors: Eliana Hiromi
authors: EH
authors: Akamine
authors: Alison
authors: A
authors: Colquhoun
authors: Maria Helena Catelli
authors: MH
authors: de Carvalho
authors: Szulim Ber
authors: SB
authors: Zyngier
authors: Zuleica Bruno
authors: ZB
authors: Fortes
mesh_terms: D000818:Animals; D002279:Carcinoma 256, Walker / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D009336:Necrosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D008687:Metformin