title: Metformin treatment modulates the tumour-induced wasting effects in muscle protein metabolism minimising the cachexia in tumour-bearing rats.
abstract: Cancer-cachexia state frequently induces both fat and protein wasting, leading to death. In this way, the knowledge of the mechanism of drugs and their side effects can be a new feature to treat and to have success, contributing to a better life quality for these patients. Metformin is an oral drug used in type 2 diabetes mellitus, showing inhibitory effect on proliferation in some neoplastic cells. For this reason, we evaluated its modulatory effect on Walker-256 tumour evolution and also on protein metabolism in gastrocnemius muscle and body composition.
  
  
  
  Wistar rats received or not tumour implant and metformin treatment and were distributed into four groups, as followed: control (C), Walker 256 tumour-bearing (W), metformin-treated (M) and tumour-bearing treated with metformin (WM). Animals were weighed three times a week, and after cachexia state has been detected, the rats were euthanised and muscle and tumour excised and analysed by biochemical and molecular assays.
  
  
  
  Tumour growth promoted some deleterious effects on chemical body composition, increasing water and decreasing fat percentage, and reducing lean body mass. In muscle tissue, tumour led to a decreased protein synthesis and an increased proteolysis, showing the higher activity of the ubiquitin-proteasome pathway. On the other hand, the metformin treatment likely minimised the tumour-induced wasting state; in this way, this treatment ameliorated chemical body composition, reduced the higher activities of proteolytic enzymes and decreased the protein waste.
  
  
  
  Metformin treatment not only decreases the tumour growth but also improves the protein metabolism in gastrocnemius muscle in tumour-bearing rats.
authors.affiliation: Department of Structural and Functional Biology, Biology Institute, State University of Campinas, UNICAMP, Rua Monteiro Lobato, 255, CP 6109, Campinas, São Paulo, 13083862, Brazil.
authors.forename: André G
authors.initials: AG
authors.lastname: Oliveira
authors.affiliation: Department of Structural and Functional Biology, Biology Institute, State University of Campinas, UNICAMP, Rua Monteiro Lobato, 255, CP 6109, Campinas, São Paulo, 13083862, Brazil. cintgoma@unicamp.br.
authors.forename: Maria Cristina C
authors.initials: MC
authors.lastname: Gomes-Marcondes
mesh_terms: D000818:Animals; D001823:Body Composition / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy*; D002279:Carcinoma 256, Walker / Q000150:complications* / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D009124:Muscle Proteins; D008687:Metformin
keywords: Cancer; Metformin; Muscle metabolism; Protein degradation; Protein synthesis; Walker-256 tumour