The effect of single bout and prolonged aerobic exercise on tumor hypoxia in mice

The objectives of this study were to investigate 1) the effect of acute aerobic exercise on tumor hypoxia and blood perfusion, 2) the impact of exercise intensity, 3) the duration of the effect, and 4) the effect of prolonged training on tumor hypoxia and tumor growth. Female CDF1 mice were inoculated with the C3H mammary carcinoma either in the mammary fat pad or subcutaneously in the back. For experiments on the effect of different intensities in a single exercise bout, mice were randomized to 30-min treadmill running at low-, moderate-, or high-intensity speeds or no exercise. To investigate the prolonged effect on hypoxia and tumor growth, tumor-bearing mice were randomized to no exercise (CON) or daily 30-min high-intensity exercise averaging 2 wk (EX). Tumor hypoxic fraction was quantified using the hypoxia marker Pimonidazole. Initially, high-intensity exercise reduced tumor hypoxic fraction by 37% compared with CON [P = 0.046; 95% confidence interval (CI): 0.1; 10.3] in fat pad tumors. Low- and moderate-intensity exercises did not. Following experiments investigating the duration of the effect-as well as experiments in mice with back tumors-failed to show any exercise-induced changes in hypoxia. Interestingly, prolonged daily training significantly reduced hypoxic fraction by 60% (P = 0.002; 95% CI: 2.5; 10.1) compared with CON. Despite diverging findings on the acute effect of exercise on hypoxia, our data indicate that if exercise has a diminishing effect, high-intensity exercise is needed. Prolonged training reduced tumor hypoxic fraction-cautiously suggesting a potential clinical potential.NEW & NOTEWORTHY This study provides novel information on the effects of acute and chronic exercise on tumor hypoxia in mice. In contrast to the few related existing studies, diverging findings on tumor hypoxia after acute exercise were observed, suggesting that tumor model and location should be considered in future studies. Highly significant reductions in tumor hypoxia following chronic high-intensity exercise propose a future clinical potential but this should be investigated in patients.