title: Protective effect of metformin against walker 256 tumor growth is not dependent on metabolism improvement.
abstract: OBJECTIVE
  The objective of the current work was to test the effect of metformin on the tumor growth in rats with metabolic syndrome.
  
  
  METHODS
  We obtained pre-diabetic hyperinsulinemic rats by neonatal treatment with monosodium L-glutamate (MSG), which were chronically treated every day, from weaning to 100 day old, with dose of metformin (250 mg/kg body weight). After the end of metformin treatment, the control and MSG rats, treated or untreated with metformin, were grafted with Walker 256 carcinoma cells. Tumor weight was evaluated 14 days after cancer cell inoculation. The blood insulin, glucose levels and glucose-induced insulin secretion were evaluated.
  
  
  RESULTS
  Chronic metformin treatment improved the glycemic homeostasis in pre-diabetic MSG-rats, glucose intolerance, tissue insulin resistance, hyperinsulinemia and decreased the fat tissue accretion. Meanwhile, the metformin treatment did not interfere with the glucose insulinotropic effect on isolated pancreatic islets. Chronic treatment with metformin was able to decrease the Walker 256 tumor weight by 37% in control and MSG rats. The data demonstrated that the anticancer effect of metformin is not related to its role in correcting metabolism imbalances, such as hyperinsulinemia. However, in morphological assay to apoptosis, metformin treatment increased programmed cell death.
  
  
  CONCLUSIONS
  Metformin may have a direct effect on cancer growth, and it may programs the rat organism to attenuate the growth of Walker 256 carcinoma.
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotecnology, Genetics and Cell Biology, State University of Maringá, Maringá/PR, Brazil.
authors.forename: Claudinéia Conationi da Silva
authors.initials: CC
authors.lastname: Franco
authors.forename: Rosiane Aparecida
authors.initials: RA
authors.lastname: Miranda
authors.forename: Júlio Cezar
authors.initials: JC
authors.lastname: de Oliveira
authors.forename: Luiz Felipe
authors.initials: LF
authors.lastname: Barella
authors.forename: Aryane Rodrigues
authors.initials: AR
authors.lastname: Agostinho
authors.forename: Kelly Valério
authors.initials: KV
authors.lastname: Prates
authors.forename: Ananda
authors.initials: A
authors.lastname: Malta
authors.forename: Amanda Bianchi
authors.initials: AB
authors.lastname: Trombini
authors.forename: Rosana
authors.initials: R
authors.lastname: Torrezan
authors.forename: Clarice
authors.initials: C
authors.lastname: Gravena
authors.forename: Laize P
authors.initials: LP
authors.lastname: Tófolo
authors.forename: Juliane Rocha
authors.initials: JR
authors.lastname: de Sant'Anna
authors.forename: Marialba Avezum Alves
authors.initials: MA
authors.lastname: de Castro Prado
authors.forename: Camila Oliveira
authors.initials: CO
authors.lastname: de Souza
authors.forename: Helenir Medri
authors.initials: HM
authors.lastname: de Souza
authors.forename: Evandro José
authors.initials: EJ
authors.lastname: Beraldi
authors.forename: Paulo Cezar de Freitas
authors.initials: PC
authors.lastname: Mathias
mesh_terms: D000818:Animals; D001786:Blood Glucose; D002279:Carcinoma 256, Walker / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D018149:Glucose Intolerance / Q000188:drug therapy / Q000473:pathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D007515:Islets of Langerhans / Q000378:metabolism; D008687:Metformin / Q000008:administration & dosage*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D012970:Sodium Glutamate / Q000633:toxicity
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D012970:Sodium Glutamate