The Effect of a Chemotherapy Drug Cocktail on Myotube Morphology and Protein Metabolism

Cachexia, a condition prevalent in many chronically-ill patients, is characterized by weight loss and fatigue resulting from decreases in muscle mass and function. Although development of cachexia is associated with tumour-burden and disease-related malnutrition, studies have suggested a causative link between chemotherapy and cachexia. Day 4 myotubes were treated with vehicle or a chemotherapy drug cocktail consisting of cisplatin, 5-fluourouracil and leucovorin. Myotubes treated with the drug cocktail showed irregular myotube structure and reductions in myofibrillar protein content. Myotubes treated with the drug cocktail showed reductions in the phosphorylation of AKTSer473, S6Ser235/236 and S6K1Thr389. Drug treatments also led to reductions in protein synthesis and mitochondrial complexes cytochrome C oxidase and succinate dehydrogenase. Lastly, reductions in insulin stimulated glucose uptake were found following drug treatment. Findings suggest that it is critical to identify interventions that limit the negative effects of these drugs on muscle protein status and mitochondrial content.