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Abstract
Lung cancer is the second most common cancer and maintains a relatively small survival rate (~20%). Non-Small Cell Lung Cancer (NSCLC) makes up 80-85% of all lung cancer diagnoses. Lung cancer patients routinely undergo surgical procedures, chemotherapy, and/or radiation and these therapies can drive ongoing systemic issues, greatly hindering patient welfare and recovery timelines. Importantly, chemotherapy and radiation can induce deleterious systemic side effects, particularly within skeletal muscle, that are not reversible even in remission. We conducted experiments to determine whether Metformin can reduce lung cancer tumor burden in immunocompetent mice while maintaining skeletal muscle health. C57BL/6 mice were given Lewis Lung Cancer (LL/2), a form of NSCLC, orthotopically into the left lung. The LL/2 cells contained a bioluminescent reporter to track tumor growth in vivo with an imaging system. Control animals received a vehicle treatment of 1x phosphate buffered saline and Metformin treated animals received a Metformin (250mg/kg) twice a week. Tumor growth was monitored over the duration of the study and analyses were conducted to assess the efficacy of Metformin as a tumor suppressor in vivo (Chapter 2). To determine whether Metformin supports skeletal muscle health in mice with NSCLC, skeletal muscle homogenates from the cancer-bearing mice were analyzed for changes in genes and proteins related to inflammation, muscle mass, and metabolism (Chapter 3). Several experiments were conducted with LL/2 cells in vitro to determine the mechanisms by which Metformin alters the oncogenic program of NSCLC (Chapter 4). Understanding mechanisms by which Metformin influences NSCLC progression could lead to potential therapeutic options for enriched targeted therapy. Importantly, assessing how Metformin may support skeletal muscle health throughout lung cancer progression could contribute clinically meaningful improvements for cancer patients.