Unveiling the role of moderate exercise training in immune system and prostate signalome: data from a rat model

Abstract

Background: Prostate cancer (PCa) is among the most prevalent cancers worldwide. This work aimed to under- stand the effects of exercise training in a rat model of PCa chemically and hormonally-induced. Material and Methods: Fifty-five male Wistar rats were divided into: control sedentary (SED+CONT; n=10), control exercised (EX+CONT; n=10), induced seden- tary (SED+PCa; n = 15) and induced exercised (EX+PCa; n=20). Exercised animals were trained in a treadmill for 53weeks. PCa induction consisted in a multistep proto- col including flutaminde and N-methyl-N-nitrosourea administration, followed by testosterone propionate im- plants. At sacrifice, dorsolateral prostate lobe and periph- eral blood was collected. Data were analysed using SPSS 25 and values were statistically significant at p < 0.05. Results: CD4+/CD8+ ratio in dorsolateral prostate tis- sue was decreased in EX+PCa group when compared to SED+PCa group. Peripheral levels of γδ T cells were higher in exercised groups (p < 0.05). The most prominent changes in prostate proteome induce by exercise were Estrogen Receptor-alpha (ERalfa; ESR1) upregulation of stimulatory Ser-104 phosphorylation (+ 1976% change from SED+PCa rats) and Mitogen-activated Protein Kinase 13 (MAPK13; p38δ MAPK) downregulation of stimulatory Thr-180 and Tyr-182 phosphorylation (-80% change from SED+PCa rats). Conclusions: Our results reinforce the beneficial role of exercise in anti-tumour immune response, with modula- tion of ER-alpha and MAPK pathways and remodelling of peripheral lymphocyte subpopulations, and lymphocyte infiltration in prostate tissue during carcinogenesis.