Experimental Clinical Oncology, Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark.
J Appl Physiol (1985). 2023 Mar 1;134(3):692-702. doi: 10.1152/japplphysiol.00561.2022. Epub 2023 Feb 2.
The objectives of this study were to investigate ) the effect of acute aerobic exercise on tumor hypoxia and blood perfusion, ) the impact of exercise intensity, ) the duration of the effect, and ) 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 [ = 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% ( = 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. 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.
本研究旨在探讨急性有氧运动对肿瘤缺氧和血液灌注的影响，包括运动强度、作用持续时间以及长期训练对肿瘤缺氧和肿瘤生长的影响。雌性 CDF1 小鼠在乳腺脂肪垫或背部皮下接种 C3H 乳腺癌。对于单次运动过程中不同强度的实验，将小鼠随机分为低、中、高强度跑步机跑步 30 分钟或不运动。为了研究对缺氧和肿瘤生长的长期影响，将荷瘤小鼠随机分为不运动（CON）或每日 30 分钟高强度运动，平均持续 2 周（EX）。使用缺氧标志物 Pimonidazole 量化肿瘤缺氧分数。最初，高强度运动使脂肪垫肿瘤的肿瘤缺氧分数降低了 37%，与 CON 相比 [ = 0.046；95%置信区间（CI）：0.1；10.3]。低强度和中等强度运动则没有。在随后的实验中，我们没有发现任何与运动相关的缺氧变化，这些实验分别探讨了作用的持续时间以及背部肿瘤的实验。有趣的是，与 CON 相比，长期每日训练使缺氧分数显著降低了 60%（ = 0.002；95%CI：2.5；10.1）。尽管关于运动对缺氧的急性影响存在分歧，但我们的数据表明，如果运动有减弱作用，高强度运动是必要的。长期训练降低了肿瘤缺氧分数——这谨慎地提示了潜在的临床潜力。本研究为小鼠急性和慢性运动对肿瘤缺氧的影响提供了新的信息。与少数相关的现有研究不同，观察到急性运动后肿瘤缺氧的结果存在差异，这表明在未来的研究中应考虑肿瘤模型和位置。慢性高强度运动后肿瘤缺氧的显著降低提示未来有临床潜力，但这需要在患者中进行研究。
