Inhibitors of COX activity preserve muscle mass in mice bearing the Lewis lung carcinoma, but not the B16 melanoma.
Tumor-induced skeletal muscle wasting (SMW) contributes to the fatigue and weakness experienced by persons with cancer cachexia. Tumor necrosis factor-alpha (TNFa) and cyclooxygenase (COX) activity have been implicated in SMW in some animal models of cancer cachexia. We report that indomethacin, a nonspecific inhibitor of COX, and NS398, a specific inhibitor of COX2, preserved muscle mass and reduced type 1 TNF receptors in muscles of mice bearing the Lewis lung carcinoma, but not in mice bearing the B16 melanoma. These data suggest that tumor-induced SMW can occur via a COX2-independent pathway. The COX2-dependent pathway may involve reducing the catabolic effects of TNFa in muscle. Further study is needed to understand the relationship between COX and SMW, and whether patients with cancer cachexia might benefit from COX inhibitors.
Laboratory of Symptom Management, National Institute of Nursing Research, Bethesda, MD, USA.
Erin
E
Graves
Edward
E
Ramsay
Donna O
DO
McCarthy
D000704:Analysis of Variance; D000818:Animals; D002100:Cachexia / Q000209:etiology / Q000517:prevention & control*; D018827:Carcinoma, Lewis Lung; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects*; D009369:Neoplasms / Q000150:complications*; D009578:Nitrobenzenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D015850:Interleukin-6; D009578:Nitrobenzenes; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D007213:Indomethacin