Losing muscle functions due to reducing muscle mass and quality is one of the main features of cancer cachexia that impairs patients' quality of life and decrease their survival. This study aimed to investigate the synergistic effects of resistance training and resveratrol supplementation on cachexia induced by CT26 tumors in male mice. Forty-eight mice were divided into eight groups randomly: healthy sedentary vehicle (HSV), healthy exercise vehicle (HEV), healthy sedentary resveratrol (HSR), healthy exercise resveratrol (HER), CT-26 tumor-bearing sedentary vehicle (TSV), CT-26 tumor-bearing exercise vehicle (TEV), CT-26 tumor-bearing sedentary resveratrol (TSR) and CT-26 tumor-bearing exercise resveratrol (TER). Training groups performed ladder climbing with weights tied to their tails, for six weeks. Resveratrol-treated groups received 50 mg/kg daily by gavage. The results showed muscle weight, and mTORC1 phosphorylation decreased in TSV compared to the HSV group. mTORC1 phosphorylation was increased in TER compared to TSV, TEV, and TSR. In addition, AMPK phosphorylation was more elevated in HER compared to HSV, HEV, and HSR. LC3BII/I ratio was higher in TSV than HSV group. Tumor volume was increased in all groups, with the lowest increase in TER group. In tumor tissue, mTORC1 phosphorylation was decreased in TER than in TSV, TEV, and TSR groups
AMPK phosphorylation and LC3BII/I ratio were increased in TSV than in TEV, TSR, and TER groups. In conclusion, the synergistic effect of resistance training and resveratrol supplementation is the most effective in reducing tumor volume. These advantages were mostly in line with molecular findings.