Article Title



Francielly Morena da Silva1, J. William Deaver1, A. Regina Cabrera1, Seongkyun Lim1, Eleanor Schrems1, Landen Saling1, Tyrone A. Washington1, Nicholas P. Greene1, FACSM

1University of Arkansas, Fayetteville, AR

Cancer Cachexia (CC) is a multifactorial syndrome commonly experienced by cancer patients, responsible for 20-40% of cancer-related deaths. Muscle atrophy, weakness, and fatigue are hallmarks of CC. Mechanisms of cachexia are not fully understood, and the impact of its progression on muscle function is not fully elucidated. Studies from our group and others suggest differences in CC between biological sexes. PURPOSE: Therefore, the purpose of this study was to investigate changes in contractile function and calcium regulators in male and female tumor-bearing mice METHODS: 69 male and 60 female 8-wk old BALB/c mice were grouped into PBS control, 10-, 15-, 20- and 25-days of tumor-bearing (10-12 animals/group). Cancer groups were injected with 1X106 C26 cells bilaterally to the hind flanks, while equal volume of PBS was injected in PBS controls (age-matched with 25-days). 48 hours prior to tissue collection, in vivo peak isometric torque and fatigability were assessed on dorsiflexors by electrophysiology, Tibialis Anterior (TA) being the biggest contributor for this movement. Peak torque curves were determined across frequencies from 10-300 Hz, and later normalized to tumor-free body weight to account for loss of mass due to CC. Fatigability was measured at 40 Hz with 120 consecutive stimuli, same normalization was performed. TA muscle was collected at each time point and mRNA content of SERCA1 and RYR1 were measured as part of calcium regulator markers. A one way-ANOVA across timepoints within each sex was performed as the global analysis with α=0.05. RESULTS: In males, peak torque was ~35% lower in 25-days vs. PBS group at 300Hz (p=0.01), while in females, peak torque was not statistically different between groups. When normalized to tumor-free body mass, statistical differences between 25-days and PBS were no longer noted in male. Lack of statistical significance remained in female mice after normalization. Same pattern was noted in fatigability. In both male and female, TA mRNA levels of SERCA1 and RYR1 were not statistically different. CONCLUSION: CC differently alters raw contractile function but not calcium regulation markers in TA of male and female mice. Yet, muscle weaknesses in CC seems to be due to loss of muscle mass and not to alterations of intrinsic contractile properties of myofibers.

ACKNOWLEDGEMENTS: Supported by NIH grant 5 R01 AR075794-02.

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