Cardio-oncology — elucidation of the mechanism of cardiac dysfunction caused by cancer therapy and cancer cachexia

Abstract

Cardiovascular disorders in cancer patients with cachexia have recently become a great concern. However, the relationship between cancer cachexia and cardiac dysfunction remains unclear, due to lack of suitable models. We established a novel murine model of cancer cachexia by implantation of 85As2 cells, a cell line derived from human gastric cancer cells, presenting anorexia, weight loss and low fat-free mass similar to those observed in patients. Moreover, cardiac dysfunction is expected in this model, which has not been yet examined. In the present study, we firstly evaluated cardiac functions with the model. Secondly, we investigated effects of voluntary wheel running (VWR) on cachexia-induced cardiac dysfunction using this model, as the exercise is considered to be one of therapies for chronic heart failure. 85As2 cells were transplanted subcutaneously into mice, which observed a symptomatic cachexia; decrease in body, skeletal muscle weight, and food intake. In addition, this cachexia mouse developed severe cardiac atrophy and left ventricular ejection fraction (LVEF) also markedly reduced with cachexia progression. Moreover, VWR suppressed the decrease in food intake and skeletal muscle weight loss in this model, and improved LVEF with suppression of heart weight loss. These results imply that our 85As2-cachexia mice models show cardiac dysfunction and VWR may improve not only cachexia symptoms but also cardiac dysfunction. As exercise therapy is generally introduced for the purpose of improving heart failure symptoms, this study suggests a possible therapeutic effect of exercise on cardiac dysfunction induced by cancer cachexia.