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

Area of Science:

• Oncology
• Exercise Physiology
• Molecular Biology

Background:

• Prostate cancer progression, particularly Castration-Resistant Prostate Cancer (CRPC), remains a significant clinical challenge.
• Understanding the molecular mechanisms underlying tumor growth is crucial for developing novel therapeutic strategies.
• The role of physical activity in cancer management is an emerging area of research.

Purpose of the Study:

• To investigate the impact of voluntary wheel running (VWR) on tumor growth in a CRPC mouse model.
• To explore the potential molecular pathways, including DNA replication, Androgen Receptor (AR) signaling, and mitochondrial dynamics, affected by VWR.

Main Methods:

• A CRPC xenograft mouse model was established using human CWR-22RV1 cells.
• Mice were divided into voluntary wheel running (VWR) and sedentary (SED) groups.
• Tumor volume was monitored, and tumor tissues were analyzed for gene and protein expression using RT-PCR, western blotting, and transcriptomics.

Main Results:

• VWR significantly reduced tumor volume and attenuated tumor progression compared to the SED group.
• Reduced tumor growth correlated with lower mRNA expression of DNA replication markers (MCM2, MCM6, MCM7) and AR signaling targets (ELOVL5, FKBP5).
• VWR also altered mitochondrial dynamics markers and downregulated pathways involved in angiogenesis and extracellular matrix formation.

Conclusions:

• Three weeks of VWR effectively delayed tumor formation and progression in this CRPC model.
• The observed benefits are associated with reduced transcription of DNA replication, AR signaling, and mitochondrial dynamics.
• Downregulation of angiogenesis pathways may contribute to the anti-tumor effects of VWR.