Voluntary Wheel Running Does Not Enhance Radiotherapy Efficiency in a Preclinical Model of Prostate Cancer: The Importance of Physical Activity Modalities?

Abstract

Simple SummaryPhysical activity is increasingly incorporated in cancer patient health care as a strategy to improve survival outcomes. However, its effects on treatment efficiency remains unclear. The aim of our preclinical study is to evaluate whether access to a running wheel could enhance the response to radiotherapy in mice with prostate cancer. We observed that voluntary wheel running (VWR) did not slow down tumor growth but appeared to modulate some parameters related to tumor perfusion. However, this did not result in enhanced response to radiotherapy. To investigate whether the lack of benefits on tumor growth observed with VWR could be attributed to the choice of physical activity modality, we conducted additional experiments comparing the effects of treadmill running versus VWR in two different preclinical models of prostate cancer. Only treadmill running was able to slow down tumor growth. Hence, the anti-cancer effects of physical activity seem dependent on its modalities.Physical activity is increasingly recognized as a strategy able to improve cancer patient outcome, and its potential to enhance treatment response is promising, despite being unclear. In our study we used a preclinical model of prostate cancer to investigate whether voluntary wheel running (VWR) could improve tumor perfusion and enhance radiotherapy (RT) efficiency. Nude athymic mice were injected with PC-3 cancer cells and either remained inactive or were housed with running wheels. Apparent microbubble transport was enhanced with VWR, which we hypothesized could improve the RT response. When repeating the experiments and adding RT, however, we observed that VWR did not influence RT efficiency. These findings contrasted with previous results and prompted us to evaluate if the lack of effects observed on tumor growth could be attributable to the physical activity modality used. Using PC-3 and PPC-1 xenografts, we randomized mice to either inactive controls, VWR, or treadmill running (TR). In both models, TR (but not VWR) slowed down tumor growth, suggesting that the anti-cancer effects of physical activity are dependent on its modalities. Providing a better understanding of which activity type should be recommended to cancer patients thus appears essential to improve treatment outcomes.