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

Abstract

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.

Combined effects of exercise and immuno-chemotherapy treatments on tumor growth in MC38 colorectal cancer-bearing mice

“…Furthermore, in the present study, the combination of exercise with immuno-chemotherapy had no effect on apoptosis at D16, whereas we expected an increase in cell death markers such as Caspase 3. One study found a potentiation of apoptosis when exercise was combined with radiotherapy compared with radiotherapy alone in a prostate cancer model (34,37). In a patient-derived xenograft (PDX) non-small-cell lung cancer model, Martıń-Ruiz et al also found that exercise in combination with PD-1 blockade reduced tumor growth, exhibiting diminished tumor cell proliferation and increase of tumor necrosis.…”