Exercise training improves radiotherapy efficiency in a murine model of prostate cancer

• Published in: The FASEB journal 2020-04, Vol.34 (4), p.4984-4996
• Main Authors: Dufresne, Suzanne, Guéritat, Jordan, Chiavassa, Sophie, Noblet, Caroline, Assi, Mohamad, Rioux‐Leclercq, Nathalie, Rannou‐Bekono, Françoise, Lefeuvre‐Orfila, Luz, Paris, François, Rébillard, Amélie
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Ly - genetics; Antigens, Ly - metabolism; Apoptosis; Caspase 3 - genetics; Caspase 3 - metabolism; Cell Line, Tumor; Combined Modality Therapy; Humans; Interleukin-2 Receptor beta Subunit - genetics; Interleukin-2 Receptor beta Subunit - metabolism; Life Sciences; Male; Mice; NK Cell Lectin-Like Receptor Subfamily B - genetics; NK Cell Lectin-Like Receptor Subfamily B - metabolism; NK Cell Lectin-Like Receptor Subfamily K - genetics; NK Cell Lectin-Like Receptor Subfamily K - metabolism; oncology; physical activity; Physical Conditioning, Animal - methods; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - radiotherapy; Prostatic Neoplasms - therapy; radiation therapy; Radiotherapy - methods; treatment
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.201901728R

Engaging in exercise while undergoing radiotherapy (RT) has been reported to be safe and achievable. The impact of exercise training (ET) on RT efficiency is however largely unknown. Our study aims to investigate the interactions between ET and RT on prostate cancer growth. Athymic mice received a subcutaneous injection of PPC‐1 cells and were randomly assigned to either cancer control, cancer ET, cancer RT, or cancer RT combined with ET (CaRT‐ET). Mice were sacrificed 24 days post‐injection. All three intervention groups had reduced tumor size, the most important decrease being observed in CaRT‐ET mice. Apoptotic marker cleaved caspase‐3 was not modified by ET, but enhanced with RT. Importantly, this increase was the highest when the two strategies were combined. Furthermore, NK1.1 staining and gene expression of natural killer (NK) cell receptors Klrk1 and Il2rβ were not affected by ET alone but were increased with RT, this effect being potentiated when combined with ET. Overall, our study shows that (a) ET enhances RT efficiency by potentiating NK cell infiltration, and (b) while ET alone and ET combined with RT both reduce tumor growth, the mechanisms mediating these effects are different.