Exercise training prior to and during cancer in mice preserves muscle mass, reduces tumour weight and suppresses molecular mediators of cachexia

Authors

• Stavroula Tsitkanou, University of Arkansas SystemFollow
• Pieter J. Koopmans, University of Arkansas System
• Ana Regina Cabrera, University of Arkansas System
• Nathan Serrano, University of Arkansas System
• Calvin S. Peterson, University of Arkansas System
• Ruqaiza Muhyudin, University of Arkansas System
• Zain B. Malik, University of Arkansas System
• Micah Goeke, University of Arkansas System
• Eleanor R. Schrems, University of Arkansas System
• Francielly Morena, University of Arkansas System
• Yuan Wen, University of KentuckyFollow
• Tyrone A. Washington, University of Arkansas System
• Kevin A. Murach, University of Arkansas SystemFollow
• Nicholas P. Greene, University of Arkansas SystemFollow

Abstract

Abstract: We investigated the prophylactic effects of exercise before and during cancer cachexia (CC) using a model designed to mimic endurance and resistance (i.e., concurrent) adaptations. Male and female Balb/c mice were randomly assigned to exercise or control groups whereby exercise groups were subjected to an 8-week voluntary progressive weighted wheel running (PoWeR) programme of habitual loading-mediated physical activity beginning at 8 weeks of age. At 16 weeks of age, mice were injected bilaterally with colon-26 adenocarcinoma (C26) cells or phosphate-buffered saline, and exercise training was maintained throughout disease progression. Twenty-five days post-tumour induction, we assessed whole-body and muscle phenotype, muscle protein synthesis, a priori targeted gene expression, and transcriptomic adaptations via RNA sequencing. PoWeR training preserved skeletal muscle mass across nearly all muscle groups and maintained tumour-free body and cardiac mass. Muscle mass adaptations related to running volume, and running distance relative to controls were not appreciably reduced by tumour status. Tumour burden was reduced after ∼11.5 weeks of PoWeR compared to sedentary, but this was not explanatory for muscle adaptations. PoWeR induced a faster-to-slower muscle fibre type transition in the gastrocnemius and suppressed key protein turnover markers (Redd1, Murf1, Atrogin, Ubc, Gadd45a) as well as the mitophagy-related marker Bnip3 in tumour-bearing muscle; 24 h muscle protein synthesis remained stable. PoWeR counteracted tumour-induced impairments in the muscle mitochondrial- and metabolic-related transcriptome. Collectively, physical activity prior to and during cancer preserves muscle mass, reduces tumour growth and mitigates molecular drivers of CC, underscoring its preventive and therapeutic potential as a lifestyle intervention. (Figure presented.). Key points: Cancer cachexia (CC) is a severe, multifactorial syndrome with limited effective therapies. Exercise training has emerged as a promising non-pharmacological approach to mitigate CC. Concurrent endurance and resistance training, initiated prior to and maintained during cancer, preserves skeletal muscle mass and reduces tumour burden in C26 colorectal tumour-bearing mice. Concurrent exercise training suppresses key mitochondrial- and metabolic-related molecular mediators of CC. Concurrent exercise training may serve as a preventive and therapeutic non-pharmacological strategy against CC.

Document Type

Article

Publication Date

7-15-2026

Notes/Citation Information

Publisher Copyright: © 2026 The Author(s). The Journal of Physiology © 2026 The Physiological Society.

Digital Object Identifier (DOI)

10.1113/JP290740

Archival?

Archival

Repository Citation

Tsitkanou, Stavroula; Koopmans, Pieter J.; Cabrera, Ana Regina; Serrano, Nathan; Peterson, Calvin S.; Muhyudin, Ruqaiza; Malik, Zain B.; Goeke, Micah; Schrems, Eleanor R.; Morena, Francielly; Wen, Yuan; Washington, Tyrone A.; Murach, Kevin A.; and Greene, Nicholas P., "Exercise training prior to and during cancer in mice preserves muscle mass, reduces tumour weight and suppresses molecular mediators of cachexia" (2026). Physiology Faculty Publications. 202.
https://uknowledge.uky.edu/physiology_facpub/202