Document Type

Dissertation/Thesis

Date Created

5-2020

Abstract

Cancer cachexia is a complex multiorgan syndrome that affects bodily systems such as liver, brain, fat tissue, and skeletal muscle. It is a major factor that decreases quality of life in cancer patients and is related to about 20% of cancer deaths, however exercise has shown to be effective in helping combat the muscle wasting effects that cancer cachexia has on the body. Cachexia characterized by skeletal muscle wasting which may be caused by downregulation of positive myogenic regulatory factors such as MyoD and myogenin, and upregulation of negative myogenic regulatory factors such as myostatin and MuRF-1. While it is known that exercise is effective in combatting skeletal muscle wasting, little is known about how different modes of exercise affect cachexia. The purpose of this study was to determine the effects of an endurance training protocol, a resistance training protocol, and a combined endurance and resistance training protocol in cancer cachexia on specific positive myogenic regulatory factors such as MyoD and myogenin, and on negative myogenic regulatory factors myostatin and MuRF-1. Six week old male Balb/c mice were randomly assigned to one of the following groups: sedentary+control (SED+Control), sedentary+tumor (SED+Tumor), treadmill training+tumor (TM+Tumor), resistance training+ tumor (RT+Tumor), and combined treadmill training and resistance training+ tumor (COMBO+Tumor). TM mice were trained on a motorized treadmill 5 days per week, RT mice had their food and water raised to an end height of 18 cm as a resistance training model, and the COMBO group used both protocols. The exercise protocols started at 6 weeks of age. At 11 weeks old, mice in the tumor groups were inoculated with C26 cells that caused cancer cachexia and were allowed to remain sedentary (SED, normal cage activity) if in SED+Tumor group; the rest of the groups continued with the exercise protocol according to their assigned group. Mice were then sacrificed at 14 weeks of age, and the gastrocnemius was excised. Western blotting was then performed to quantify the expression of MyoD, myogenin, myostatin, and MuRF-1. A one-way ANOVA found a significant difference between groups for myostatin expression (F=4.383, Ppost hoctesting revealed that SED+Tumor had a significantly higher myostatin expression than TM+Tumor, RT+Tumor, and COMBO+Tumor. No significant group differences were observed for MyoD (F=2.389, p>0.05), myogenin (F=.799, p>0.05), or MuRF-1 expression (F=1.03, p>0.05). The main finding of this study was that exercised tumor bearing animals had significantly less myostatin than sedentary tumor bearing mice suggesting that any mode of exercise could have a protective effect on skeletal muscle. Because the decrease was evident regardless of exercise mode, including endurance training, resistance training, or combined endurance and resistance training may help combat the negative effects of cachexia through the suppression of the negative myogenic regulatory factor myostatin.

Keywords

cancer cachexia: myogenic regulatory factors: muscle wasting: myostatin: myogenin: MuRF-1: MyoD

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