title: Distinct behaviour of sorafenib in experimental cachexia-inducing tumours: the role of STAT3.
abstract: The presence of a tumour is very often associated with wasting in the host, affecting both skeletal muscle and adipose tissue. In the present study we used sorafenib, a multi-kinase inhibitor with anti-tumour activity, in order to investigate the effects of chemotherapy on wasting. Three different experimental mouse tumour models were included: C26 colon carcinoma, B16 melanoma and Lewis lung carcinoma (LLC). The results obtained clearly show that sorafenib was effective in reducing tumour growth in LLC and B16 models, while it had no effect on C26. Interestingly, sorafenib treatment reduced the signs of muscle wasting and improved the physical activity in the LLC model and also in the C26, despite the absence of antineoplastic action in the latter. Our results discard a role for IL-6 in the action of sorafenib since the drug did not affect the levels of this cytokine. Conversely, sorafenib seems to act by influencing both STAT3 and ERK activity at muscle level, leading to reduced accumulation of Pax7 and atrogin-1. Sorafenib may interfere with muscle wasting by decreasing the activation of these signal transduction pathways.
authors.affiliation: Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Míriam
authors.initials: M
authors.lastname: Toledo
authors.affiliation: Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Department of Clinical and Biological Sciences, University of Torino, Turin, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Penna
authors.affiliation: Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Busquets
authors.affiliation: Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: López-Soriano
authors.affiliation: Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Argilés
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002100:Cachexia / Q000150:complications* / Q000188:drug therapy; D018827:Carcinoma, Lewis Lung / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D000077157:Sorafenib; D019282:Wasting Syndrome / Q000150:complications / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D050796:STAT3 Transcription Factor; D009536:Niacinamide; D000077157:Sorafenib