Abstract
BackgroundAltering the systemic milieu through exercise has been proposed as a potential mechanism underlying exercise-driven tumour suppression. It is not yet known whether men with advanced prostate cancer can elicit such adaptations following a program of exercise. The purpose is to examine myokine levels of serum acquired from metastatic castrate-resistant prostate cancer (mCRPC) patients recruited to the INTERVAL-GAP4 trial before and after 6 months of exercise and its tumour-suppressive effect.MethodsTwenty-five men with mCRPC (age = 74.7 ± 7.1 yrs) were randomised to supervised multimodal (aerobic and resistance) exercise (EX) or self-directed exercise control group (CON). Body composition was assessed using dual-energy x-ray absorptiometry (DXA), and fasting blood in a rested state was collected at baseline and at 6 months. Serum levels of myokines (SPARC, OSM, decorin, IGF-1, and IGFBP-3) were measured. Serum was applied to the prostate cancer cell line DU145, and growth was assessed for 72 h.ResultsNo significant change in body composition was observed. Adjusted serum OSM (P = 0.050) and relative OSM (P = 0.083), serum SPARC (P = 0.022) and relative SPARC (P = 0.025) increased in EX compared to CON. The area under curve (AUC) over 72 h showed a significant reduction in DU145 growth after applying post-intervention serum from the EX vs CON (P = 0.029).ConclusionElevated myokine expressions and greater tumour-suppressive effects of serum after 6 months of periodised and autoregulated supervised exercise was observed in men with mCRPC. Exercise-induced systemic changes may slow disease progression in men with advanced prostate cancer.
Highlights
Exercise has been established as effective in improving physical function and supportive care outcomes for cancer patients, including those with advanced disease [1]
Exercise induces multiple physiological changes, including alteration in cell-free and soluble molecules in the circulatory system known to have tumour-suppressive effects [5]. This has been further demonstrated in studies in which resting serum acquired after longterm exercise programs or exercise-conditioned serum obtained after a single bout of exercise applied to cancer cell lines produces substantial suppression of growth [7–13], with evidence supporting the involvement of exercise-induced serological insulin-like growth factor-1 (IGF-1) axis alteration in prostate cancer cell growth suppression [7, 11–13]
In our recent report [14], we showed suppression of androgen-independent prostate cancer cell line DU145 growth by applying serum acquired from patients with localised prostate cancer undergoing androgen deprivation therapy (ADT) following a 3-month exercise intervention and observed alterations in circulating cell-free/soluble factors compared to a pretrained state, suggesting a potential of exercise in prostate cancer suppression [5]
Summary
Altering the systemic milieu through exercise has been proposed as a potential mechanism underlying exercisedriven tumour suppression. It is not yet known whether men with advanced prostate cancer can elicit such adaptations following a program of exercise. The purpose is to examine myokine levels of serum acquired from metastatic castrate-resistant prostate cancer (mCRPC) patients recruited to the INTERVAL-GAP4 trial before and after 6 months of exercise and its tumour-suppressive effect. CONCLUSION: Elevated myokine expressions and greater tumour-suppressive effects of serum after 6 months of periodised and autoregulated supervised exercise was observed in men with mCRPC. Exercise-induced systemic changes may slow disease progression in men with advanced prostate cancer.
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