Abstract
Loss of muscle mass related to anti-cancer therapy is a major concern in cancer patients, being associated with important clinical endpoints including survival, treatment toxicity and patient-related outcomes. We investigated effects of voluntary exercise during cisplatin treatment on body weight, food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatment induced loss of body weight (29.8%, P<0.001), lean body mass (20.6%, P = 0.001), as well as anorexia, impaired muscle strength (22.5% decrease, P<0.001) and decreased glucose tolerance. In addition, cisplatin impaired Akt-signalling, induced genes related to protein degradation and inflammation, and reduced muscle glycogen content. Voluntary wheel running during treatment attenuated body weight loss by 50% (P<0.001), maintained lean body mass (P<0.001) and muscle strength (P<0.001), reversed anorexia and impairments in Akt and protein degradation signalling. Cisplatin-induced muscular inflammation was not prevented by voluntary wheel running, nor was glucose tolerance improved. Exercise training may preserve muscle mass in cancer patients receiving cisplatin treatment, potentially improving physical capacity, quality of life and overall survival.
Highlights
Loss of muscle mass is a common clinical finding across cancer diagnoses and stages attributable to a range of factors related to both anti-cancer treatment, patient lifestyle and the cancer disease itself [1]
Exercise ameliorates effects of cisplatin on body weight, lean mass, food intake and strength Six weeks of cisplatin treatment induced a 29.8% loss of body weight (P,0.001, n = 16) compared to pre-treatment levels in sedentary mice (FIG. 1A), and these mice weighed 43% less than control mice
Weight reductions of 22.362.4 mg tibialis anterior (TA) muscle and 65.467.0 mg heart was found in sedentary cisplatin-treated mice compared with controls (FIG. 1D–E), and sedentary cisplatin-treated mice had an average of two falls during the 3 min hang test, compared to no falls in saline control mice (P,0.001, CON: n = 8, EX: n = 9) (FIG. 1F)
Summary
Loss of muscle mass is a common clinical finding across cancer diagnoses and stages attributable to a range of factors related to both anti-cancer treatment, patient lifestyle and the cancer disease itself [1] In both patients with early and advanced stage disease, muscle mass significantly impacts patient-reported and clinical outcomes, including survival and disease progression. Doxorubicin, exercise has been shown to reverse doxorubicin-induced oxidative stress by induction of muscular antioxidant enzymes and heat shock protein 72 [11]. Evidence of such direct protective mechanisms of exercise remains to be determined for other chemotherapeutics including cisplatin
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