Exercise-induced lung cancer regression: Mechanistic findings from a mouse model

Authors

  • Kristin A. Higgins MD,

    Corresponding author
    1. Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
    • Corresponding authors: Kristin A. Higgins, MD, 1365 Clifton Road NE, Atlanta, GA, 30322; Fax: (404) 778-4139; kristin.higgins@emory.edu; or Xingming Deng, MD, PhD, 1365 Clifton Road NE, Atlanta, GA, 30322; Fax: (404) 778-1909; xdeng4@emory.edu

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    • The first two authors contributed equally to this work.

  • Dongkyoo Park PhD,

    1. Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
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    • The first two authors contributed equally to this work.

  • Gee Young Lee PhD,

    1. Department of Biomedical Engineering, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Walter J. Curran MD,

    1. Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Xingming Deng MD, PhD

    Corresponding author
    1. Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
    • Corresponding authors: Kristin A. Higgins, MD, 1365 Clifton Road NE, Atlanta, GA, 30322; Fax: (404) 778-4139; kristin.higgins@emory.edu; or Xingming Deng, MD, PhD, 1365 Clifton Road NE, Atlanta, GA, 30322; Fax: (404) 778-1909; xdeng4@emory.edu

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  • This study demonstrates that daily cardiovascular exercise reduces lung tumor growth in mice, and tumor apoptosis is increased. Therefore, exercise should be explored further as a potential anticancer therapy.

  • Presented as a mini oral abstract at the 15th World Conference on Lung Cancer; October 27-30, 2013; Sydney, Australia.

Abstract

BACKGROUND

It has been demonstrated that regular exercise improves the quality of life in patients undergoing treatment for lung cancer and has been associated with reductions in cancer-specific mortality in patients with colon and breast cancer. The direct effects of cardiovascular exercise on lung cancer tumor biology, however, remain unknown. The authors evaluated the effects of cardiovascular exercise in a mouse model of lung adenocarcinoma.

METHODS

Luciferase-tagged A549 lung adenocarcinoma cells were injected through the tail vein of nude male mice. Then, the mice underwent weekly bioluminescent imaging until lung tumors were clearly identified. After lung tumors were identified, the mice were randomized to daily wheel running versus no wheel running, and they were imaged weekly. After 4 weeks, all mice were killed, and the lung tumors were harvested. Western blot and immunohistochemical analyses were conducted on tumor tissues to identify potential differences in protein expression levels in exercising mice versus sedentary mice.

RESULTS

Lung tumors in exercising mice grew significantly more slowly relative to sedentary mice. There was no change in the development of metastatic lesions between the 2 groups. Protein analysis by Western blot or immunohistochemical analysis demonstrated increased p53 protein levels in exercising mice relative to sedentary mice as well as increased mediators of apoptosis, including Bax and active caspase 3, in tumor tissues. In both groups of mice, no normal tissue toxicity was observed in other organs.

CONCLUSIONS

Daily cardiovascular exercise appears to mitigate the growth of lung adenocarcinoma tumors, possibly by activation of the p53 tumor suppressor function and increased apoptosis. Cancer 2014;120:3302–3310. © 2014 American Cancer Society.

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