Indomethacin and ibuprofen preserve gastrocnemius muscle mass in mice bearing the colon-26 adenocarcinoma.
Skeletal muscle wasting is a prominent feature of cancer cachexia and involves decreased muscle protein synthesis and increased activity of the ubiquitin-proteasome pathway of protein degradation. We report that both indomethacin and ibuprofen improved body weight and weight of the gastrocnemius muscle in tumor-bearing mice. Ibuprofen increased the soluble protein content of the muscle without affecting muscle levels of phosphorylated p70 S6 kinase, a ribosomal kinase involved in protein synthesis. Paradoxically, indomethacin increased levels of ubiquitin-conjugated proteins. Further study is needed to understand the mechanism of action by which indomethacin and ibuprofen preserve body weight and muscle mass in the tumor-bearing mice. The data suggest that ibuprofen may have beneficial effects in the treatment of cancer cachexia.
McCarthy
Donna O
DO
National Institute of Nursing Research, National Institutes of Health, 31 Center Drive, Rm. 5B13, Bethesda, MD 20892, USA.
Whitney
Pamela
P
Hitt
Andrew
A
Al-Majid
Sadeeka
S
D000230:Adenocarcinoma / Q000150:complications / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology; D003110:Colonic Neoplasms / Q000150:complications / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007052:Ibuprofen / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use*; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000150:complications / Q000473:pathology; D014451:Ubiquinone / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014451:Ubiquinone; D007052:Ibuprofen; D007213:Indomethacin