Ibuprofen ameliorates fatigue- and depressive-like behavior in tumor-bearing mice.
OBJECTIVE
Cancer-related fatigue (CRF) is often accompanied by depressed mood, both of which reduce functional status and quality of life. Research suggests that increased expression of pro-inflammatory cytokines is associated with skeletal muscle wasting and depressive- and fatigue-like behaviors in rodents and cancer patients. We have previously shown that treatment with ibuprofen, a nonsteroidal anti-inflammatory drug, preserved muscle mass in tumor-bearing mice. Therefore, the purpose of the present study was to determine the behavioral effects of ibuprofen in a mouse model of CRF.


METHODS
Mice were injected with colon-26 adenocarcinoma cells and treated with ibuprofen (10mg/kg) in the drinking water. Depressive-like behavior was determined using the forced swim test (FST). Fatigue-like behaviors were determined using voluntary wheel running activity (VWRA) and grip strength. The hippocampus, gastrocnemius muscle, and serum were collected for cytokine analysis.


RESULTS
Tumor-bearing mice showed depressive-like behavior in the FST, which was not observed in mice treated with ibuprofen. VWRA and grip strength declined in tumor-bearing mice, and ibuprofen attenuated this decline. Tumor-bearing mice had decreased gastrocnemius muscle mass and increased expression of IL-6, MAFBx and MuRF mRNA, biomarkers of protein degradation, in the muscle. Expression of IL-1β and IL-6 was also increased in the hippocampus. Treatment with ibuprofen improved muscle mass and reduced cytokine expression in both the muscle and hippocampus of tumor-bearing mice.


CONCLUSIONS
Ibuprofen treatment reduced skeletal muscle wasting, inflammation in the brain, and fatigue- and depressive-like behavior in tumor-bearing mice. Therefore, ibuprofen warrants evaluation as an adjuvant treatment for CRF.
Department of Neuroscience, The Ohio State University, United States.
Diana M
DM
Norden
College of Nursing, Marquette University, United States.
Donna O
DO
McCarthy
Division of Biosciences, College of Dentistry, The Ohio State University, United States.
Sabahattin
S
Bicer
Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, United States.
Raymond D
RD
Devine
Division of Biosciences, College of Dentistry, The Ohio State University, United States.
Peter J
PJ
Reiser
Department of Neuroscience, The Ohio State University, United States; Institute for Behavioral Medicine Research, The Ohio State University, United States.
Jonathan P
JP
Godbout
College of Nursing, The Ohio State University, United States; Department of Physiology and Cell Biology, The Ohio State University, United States. Electronic address: loren.wold@osumc.edu.
Loren E
LE
Wold
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003863:Depression / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D005221:Fatigue / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D005260:Female; D007052:Ibuprofen / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen
Cancer; Depression; Fatigue; Ibuprofen; Neuroinflammation