COMPARING THE EFFECT OF THREE EXERCISE INTERVENTIONS ON PANCREATIC TUMOR GROWTH IN MICE MODEL

Pancreatic cancer is a highly lethal disease with only a 9% five-year survival rate. It is the fourth leading cause of cancer-related death in the United States. Pancreatic cancer patients often experience reduced fitness and strength, which limits treatment options and diminishes quality of life. Exercise training yields improvements in physical function and reduces fatigue among pancreatic cancer patients. In well-studied cancers, such as breast cancer, different exercise protocols (that is, training programs differing in exercise duration, frequency, type, and intensity) have been compared and results suggest that longer duration moderate-intensity exercise might improve patient outcomes such as quality of life (QoL). However, no study has yet compared different exercise interventions for people with pancreatic cancer. Thus, identifying an optimal exercise intervention remains a critical area to improve pancreatic patients’ outcomes. In animal studies, there is also some evidence that exercise may slow tumor growth. Unfortunately, translation to the clinic has remained limited. This is due in part to the majority of the literature finding a benefit from exercise training when it has been used pre-emptively, not initiated after tumor development. Secondly, exercise-interventions have frequently been compared to no intervention at all, rather than in addition to conventional cancer treatments such as chemotherapy. Third, no study has yet compared the effects of different exercise interventions on pancreatic tumor outcomes. Therefore, in this dissertation we investigated the effect of the three exercise interventions; continuous moderate intensity-Low volume (Cont-LV), continuous moderate intensity-high volume (Cont-HV), and high intensity interval training (HIIT) on pancreatic tumor growth in mice. Exercise training was initiated after tumor development and was provided alongside chemotherapy for approximately two weeks. Exercise training may enhance immune cell infiltration into tumors as well as immune cell cytotoxicity, potentially explaining slower tumor growth in exercise-trained animals. Therefore, the second aim of this study was to investigate the effects of the three exercise interventions on immune cell tumor infiltration and function. As the vast majority of the existing literature has investigated the effect of exercise on tumor growth without chemotherapy, we also compared the effects of the three exercise interventions on tumor growth and immune cell infiltration and function in mice not receiving gemcitabine. We report no difference in tumor volume between the exercise groups and sedentary mice in the experiments that provided gemcitabine treatment. In contrast, we did find an effect of exercise in tumor-bearing mice not treated with gemcitabine, apparently driven by the tumor-inhibiting effect of continuous low-volume exercise. These effects were accompanied by an increase in the CD8+ T-cells in tumors in the continuous low volume exercise group. Overall, the results suggest that two-week long exercise interventions do not provide further benefit on tumor growth or immune function in pancreatic tumor bearing mice receiving chemotherapy. The results also support that exercise can suppress pancreatic tumor growth, potentially by promoting CD8+ T-cell infiltration in tumors in mice not receiving chemotherapy. Future research should explore the effects of longer exercise interventions as well as the effects of the timing of the exercise intervention on tumor growth and anti-tumor immune activity.Health and Human Performance, Department o