The Effects that Non-steroidal Anti-inflammatory Drugs (NSAID) have on Cancer Related Fatigue in a Mouse Model

Abstract

Purpose: Fatigue is a debilitating symptom in cancer patients. It is believed that skeletal muscle wasting is a main cause of cancer related fatigue (CRF). As of now, there is no effective treatment of CRF. According to the 2009-2013 Research Agenda of the Oncology Nursing Society, a high priority in cancer research is symptom management. There is some evidence that nonsteriodal anti-inflammatory drugs (NSAIDs) reduce muscle wasting in tumor-bearing mice. The purpose of this study is to determine the effects of ibuprofen, an NSAID, on fatigue, muscle mass, and biomarkers of muscle protein breakdown in mice bearing the Lewis lung carcinoma. In mice, fatigue is measured as a decrease in voluntary wheel running activity (VMRA) relative to a baseline. Sample and methods: The sample is 24 adult, age-matched female C57BI/6 mice. The mice were acclimated to the cages and wheels for 7 days. On day one, half of the mice were inoculated with tumor cells and half served as healthy controls. Half of each group were implanted with a pellet designed to release 5 mg/kg/day Ibuprofen over the course of 21 days of tumor-growth or a placebo pellet. The 4 groups are tumor/placebo pellet, tumor/ibuprofen pellet, no tumor/placebo pellet, no tumor/ibuprofen pellet. VWRA, body weight, food and water intake were measured on days 0, 7, 14, and 19 of tumor growth. Mice were euthanized on day 20 and the gastrocnemius muscle was removed and weighed. Results: Ibuprofen had no significant effect on VWRA, muscle mass, or biomarkers of muscle protein degradation. There was a significant negative relationship between spleen size, an indicator of systemic inflammation, and muscle mass (-.53), and a significant positive relationship between spleen size and biomarkers of muscle protein degradation (.6), and between VWRA and muscle mass (.4). These data confirm that skeletal muscle wasting is related to inflammation, and muscle wasting contributes to fatigue. More research is needed to develop effective interventions to reduce muscle wasting in patients with cancer-related fatigue.