Effects of CRF2R agonist on tumor growth and cachexia in mice implanted with Lewis lung carcinoma cells.
Previous studies have demonstrated an effect of corticotropin-releasing factor 2 receptor (CRF2R) agonists in the maintenance of skeletal muscle mass. The aim of this study was to evaluate the effects of a CRF2R agonist in preserving skeletal muscle in a mouse cachexia model. Implantation of a fast-growing tumor to mice (Lewis lung carcinoma) resulted in a clear cachectic state characterized by a profound muscle wasting. We found that administration of a CRF2R agonist (PG-873637) at 100 microg/kg/day by means of osmotic minipumps to tumor-bearing mice resulted in beneficial effects on muscle weight loss. Thus, muscle loss was partially reversed by the CRF2R agonist at different stages of tumor growth (at day 14 after tumor inoculation: 12% in tibialis posterior; 9% in gastrocnemius; and 48% in soleus). Moreover, the CRF2R agonist significantly reduced both the number of metastases and their mass (at day 19 after tumor inoculation: 66% and 61%, respectively). These data suggest a potentially beneficial effect of the CRF2R agonist in preserving skeletal muscle during cancer cachexia and open a line of research for the development of new therapeutic approaches for the treatment of muscle wasting associated with cancer.
Argilés
Josep M
JM
Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, Barcelona 08028, Spain.
Figueras
Maite
M
Ametller
Elisabet
E
Fuster
Gemma
G
Olivan
Mireia
M
de Oliveira
Cibely Cristine Fontes
CC
López-Soriano
Francisco J
FJ
Isfort
Robert J
RJ
Busquets
Sílvia
S
D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D000818:Animals; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000819:agonists*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009368:Neoplasm Transplantation / Q000379:methods; D009929:Organ Size / Q000187:drug effects; D018019:Receptors, Corticotropin-Releasing Hormone; D018709:Statistics, Nonparametric; D013997:Time Factors
C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone