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Updated: Jul 11, 2026
Murine Prostate Micro-dissection and Surgical Castration
Published on: May 11, 2016
Voluntary Exercise Attenuates Tumor Growth in a Preclinical Model of Castration-Resistant Prostate Cancer
Nicolas Berger1, Benjamin Kugler1, Dong Han
1Department of Exercise and Health Sciences, Manning College of Nursing and Health Sciences, University of Massachusetts Boston, Boston, MA.
Purpose:
To examine the effects of voluntary wheel running on tumor growth and explore potential intratumoral molecular pathways responsible for the beneficial effects of voluntary wheel running on tumor formation 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 assigned to either voluntary wheel running (VWR) or sedentary (SED) group ( n = 6/group). Tumor size was measured and calculated throughout the study. After 3 wk, tumor tissues were collected. mRNA expression of markers of DNA replication, androgen receptor (AR) signaling, and mitochondrial dynamics was determined by quantitative real-time polymerase chain reaction. Protein expression of mitochondrial dynamics was determined by Western blotting. Finally, transcriptomics analysis was performed using 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 the VWR group coincided with lower mRNA expression of DNA replication markers ( MCM2 , MCM6 , and MCM7 ), AR signaling ( ELOVL5 and FKBP5 ), and regulatory proteins of mitochondrial fission (Drp1 and Fis1) and fusion (MFN1 and OPA1) when compared with the SED group ( P < 0.05). RNA sequencing data further revealed that pathways related to angiogenesis, extracellular matrix formation, and endothelial cell proliferation were downregulated.
Conclusions:
Three weeks of voluntary wheel running was effective in delaying tumor formation and progression, which coincided with reduced transcription of DNA replication, AR signaling targets, and mitochondrial dynamics. We further identified a downregulation in molecular pathways related to angiogenesis that may be responsible for the delayed tumor formation and progression by voluntary wheel running.
Insights
Voluntary wheel running reduced tumor growth in a mouse model of Castration-Resistant Prostate Cancer (CRPC). This exercise delayed tumor progression by downregulating DNA replication, Androgen Receptor (AR) signaling, and angiogenesis pathways.
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.
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