Interdisciplinary Program in Nutritional Sciences, University of Washington, Seattle, Washington, United States of America ; Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America.
PLoS One. 2013 Nov 27;8(11):e80123. doi: 10.1371/journal.pone.0080123. eCollection 2013.
Epidemiological research suggests that regular physical activity confers beneficial effects that mediate an anti-tumor response and may reduce cancer recurrence. It is unclear what amount of physical activity is necessary to exert such a protective effect and what mechanisms are involved. We investigated the effects of voluntary wheel running on tumor progression and cytokine gene expression in the transgenic polyoma middle T oncoprotein (PyMT) mouse model of invasive breast cancer. Runners showed significantly reduced tumor sizes compared with non-runners after 3 weeks of running (p ≤ 0.01), and the greater the running distance the smaller the tumor size (Pearson's r = -0.61, p ≤ 0.04, R(2) = 0.38). Mice running greater than 150 km per week had a significantly attenuated tumor size compared with non-runners (p ≤ 0.05). Adipose tissue mass was inversely correlated with tumor size in runners (Pearson's r = -0.77, p = 0.014) but not non-runners. Gene expression of CCL22, a cytokine associated with recruitment of immunosuppressive T regulatory cells, was decreased in tumors of runners compared to non-runners (p ≤ 0.005). No differences in tumor burden or metastatic burden were observed between runners and non-runners after ten weeks of running when the study was completed. We conclude that voluntary wheel running in PyMT mice correlates with an attenuation in tumor progression early during the course of invasive breast cancer. This effect is absent in the later stages of overwhelming tumor burden even though cytokine signaling for immunosuppressive regulatory T cells was down regulated. These observations suggest that the initiation of moderate exercise training for adjunctive therapeutic benefit early in the course of invasive breast cancer should be considered for further investigation.
流行病学研究表明，有规律的体育活动对肿瘤具有有益的影响，可介导抗肿瘤反应，并可能降低癌症复发的风险。目前尚不清楚需要进行多少体育活动才能发挥这种保护作用，以及涉及哪些机制。我们研究了自愿轮式跑步对转基因多瘤病毒中 T 抗原（PyMT）小鼠模型浸润性乳腺癌进展和细胞因子基因表达的影响。与不跑步的小鼠相比，跑步的小鼠在跑步 3 周后肿瘤体积明显减小（p≤0.01），且跑步距离越大肿瘤体积越小（皮尔逊相关系数 r=-0.61，p≤0.04，R²=0.38）。每周跑步超过 150 公里的小鼠与不跑步的小鼠相比，肿瘤体积明显减小（p≤0.05）。跑步者的脂肪组织质量与肿瘤大小呈负相关（皮尔逊相关系数 r=-0.77，p=0.014），而不跑步者则没有相关性。与不跑步的小鼠相比，跑步者的肿瘤组织中细胞因子 CCL22 的基因表达降低（p≤0.005），CCL22 与免疫抑制性调节 T 细胞的募集有关。在完成 10 周跑步研究后，跑步者和不跑步者的肿瘤负担或转移负担没有差异。我们的结论是，PyMT 小鼠的自愿轮式跑步与浸润性乳腺癌早期肿瘤进展的减弱相关。即使免疫抑制性调节 T 细胞的细胞因子信号被下调，在肿瘤负担过重的晚期，这种作用仍然不存在。这些观察结果表明，对于浸润性乳腺癌早期的辅助治疗，应考虑适度运动训练的启动，以进一步研究。
