Voluntary Exercise Attenuates Tumor Growth in a Preclinical Model of Castration-Resistant Prostate Cancer.

Purpose: To examine the effects of voluntary exercise training on tumor growth and explore the underlying intratumoral molecular pathways and processes responsible for the beneficial effects of VWR on tumor initiation and progression in a mouse model of Castration-Resistant Prostate Cancer (CRPC). Methods: Male immunodeficient mice (SCID) were castrated and subcutaneously inoculated with human CWR-22RV1 cancer cells to construct CRPC xenograft model before randomly assigned to either voluntary wheel running (VWR) or sedentary (SED) group (n=6/group). After three weeks, tumor tissues were collected. Tumor size was measured and calculated. mRNA expression of markers of DNA replication, Androgen Receptor (AR) signaling, and mitochondrial dynamics was determined by RT-PCR. Protein expression of mitochondrial content and dynamics was determined by western blotting. Finally, RNA-sequencing analysis was performed in the tumor tissues. Results: Voluntary wheel running resulted in smaller tumor volume at the initial stage and attenuated tumor progression throughout the time course (P < 0.05). The reduction of tumor volume in VWR group was coincided with lower mRNA expression of DNA replication markers ( Conclusions: Three weeks of VWR was effective in delaying tumor initiation and progression, which coincided with reduced transcription of DNA replication, AR signaling targets and mitochondrial dynamics. We further identified reduced molecular pathways/processes related to angiogenesis that may be responsible for the delayed tumor initiation and progression by VWR.