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

Abstract

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.

Exercise modulation of tumour perfusion and hypoxia to improve radiotherapy response in prostate cancer

“…Radiotherapy further caused an increase in natural killer cell infiltration and activity that resulted in increased tumour cell apoptosis. Interestingly, this response was potentiated when exercise was combined with radiotherapy [80]. These results are exciting and provide preliminary preclinical evidence on the application of exercise as an adjunct therapy during radiotherapy in PCa.…”

“…To date, only one study has investigated the effect of exercise in combination with radiotherapy on treatment outcomes [80]. Dufresne et al injected human PCa PPC-1 cells subcutaneously into male athymic nude mice and subjected them to exercise 5 days/week for 25-60 min/day over 2 weeks in combination with a total of 20 Gray (Gy) fractionated into four doses of 5 Gy each.…”

Natural killer cell mobilization and egress following acute exercise in men with prostate cancer

“…Prostate cancer treatments also appear to directly influence immune function. For example, radiotherapy decreases leukocyte and lymphocyte counts (Hojan et al., 2016), but when combined with exercise training there was greater natural killer (NK) cell infiltration and reduced tumour volume (Dufresne et al., 2020). One year of ADT increased naïve CD4 T cell proportions and overall proliferation initially but not long term (Morse & McNeel, 2010), while NK cell counts nearly doubled following short‐term ADT that was prevented with testosterone replacement (Page et al., 2006).…”

Efeitos do treinamento físico aeróbio sobre a regulação dos microRNAs no tumor do câncer de cólon

“…Além disso, a combinação do exercício com a radioterapia induziu uma maior redução do crescimento tumoral em comparação aos camundongos apenas exercitados. Entretanto, a radioterapia per se reduziu o crescimento tumoral de maneira similar à combinação exercício mais radioterapia(DUFRESNE et al, 2020). O exercício per se também induziu uma redução significativa da proliferação celular tumoral (imunofluorescência para Ki67) e uma tendência de redução na % de áreas necróticas tumorais (H&E), sendo que a vascularização tumoral não foi alterada pelo exercício (imuno-histoquímica para CD31).…”

“…Por fim, o exercício potencializou os efeitos da radioterapia sobre esses marcadores analisados. Importante salientar que os efeitos do exercício sobre o crescimento tumoral também foram independentes de respostas do sistema imune adaptativo, uma vez que foram usados animais imunodeficientes NUDE(DUFRESNE et al, 2020).Por fim,Hwang et al (2020) avaliaram os efeitos de uma sessão aguda de exercício sobre a viabilidade das células tumorais humanas do câncer de próstata. Para isso, as células tumorais humanas do câncer de próstata andrógena responsiva, LNCaP, e andrógena não responsiva, PC3, foram incubadas com o soro de indivíduos saudáveis jovens e idosos em repouso ou após uma sessão aguda de exercício aeróbio.…”