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D. Park



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    MO04 - Lung Cancer Biology I (ID 86)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
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      MO04.09 - Exercise Induced Lung Cancer Tumor Growth Suppression via Activation of p53: Mechanistic Findings from a Mouse Model (ID 182)

      16:15 - 17:45  |  Author(s): D. Park

      • Abstract
      • Presentation
      • Slides

      Background
      Regular exercise has been shown to improve 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. This study evaluated cardiovascular exercise in a mouse model of lung adenocarcinoma, including clinically relevant endpoints such as lung tumor growth and distant metastasis. Furthermore, biologic mechanisms of action underlying clinical findings were also explored.

      Methods
      Luciferase-tagged A549 lung adenocarcinoma cells were injected through the tail vein of nude male mice. Mice underwent weekly bioluminescent imaging until lung tumors were clearly identified. After lung tumors were identified, mice were randomized to daily wheel-running versus no wheel-running. Mice were imaged weekly. After 4 weeks, all mice were euthanized and lung tumors were harvested. Western blots and immunohistochemistry (IHC) studies were undertaken on tumor tissue to identify potential differences in protein expression levels in exercise versus sedentary mice.

      Results
      Exercising mice tumors grew significantly more slowly relative to sedentary mice (figure 1). There was no change in development of metastatic lesions between the two groups. Protein analysis by Western blot or IHC demonstrated increased p53 protein levels in exercising mice relative to sedentary mice, as well as increased mediators of apoptosis including Bax, Bak and active caspase 3 in tumor tissues (figure 2 and data not shown). No normal tissue toxicity in other organs was observed in the two groups of mice. Figure 1. Figure 1 Figure 2. Figure 2

      Conclusion
      Daily cardiovascular exercise appears to mitigate growth of lung adenocarcinoma tumors by activation of p53 tumor suppressor function and increased apoptosis.

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