Abstract
Non-small-cell lung cancer (NSCLC) makes up 80–85% of lung cancer diagnoses. Lung cancer patients undergo surgical procedures, chemotherapy, and/or radiation. Chemotherapy and radiation can induce deleterious systemic side effects, particularly within skeletal muscle. To determine whether metformin reduces NSCLC tumor burden while maintaining skeletal muscle health, C57BL/6J mice were injected with Lewis lung cancer (LL/2), containing a bioluminescent reporter for in vivo tracking, into the left lung. Control and metformin (250 mg/kg) groups received treatments twice weekly. Skeletal muscle was analyzed for changes in genes and proteins related to inflammation, muscle mass, and metabolism. The LL/2 model effectively mimics lung cancer growth and tumor burden. The in vivo data indicate that metformin as administered was not associated with significant improvement in tumor burden in this immunocompetent NSCLC model. Additionally, metformin was not associated with significant changes in key tumor cell division and inflammation markers, or improved skeletal muscle health. Metformin treatment, while exhibiting anti-neoplastic characteristics in many cancers, appears not to be an appropriate monotherapy for NSCLC tumor growth in vivo. Future studies should pursue co-treatment modalities, with metformin as a potentially supportive drug rather than a monotherapy to mitigate cancer progression.
Highlights
Lung cancer is the second most common cancer and represents ~13% of all new cancer cases in the United States (SEER, National Cancer Institute)
We have investigated whether metformin treatment suppresses tumor growth in C57BL/6J mice with Non-small-cell lung cancer (NSCLC), and we have investigated the effects of NSCLC tumor progression on skeletal muscle health
The present study aimed to assess the effects of metformin as a stand-alone, i.e., monotherapy treatment in altering LL/2 non small lung tumor progression and its ability to support skeletal muscle health during LL/2 tumor progression in C57BL/6J mice
Summary
Lung cancer is the second most common cancer and represents ~13% of all new cancer cases in the United States (SEER, National Cancer Institute). Lung cancer contributed to ~145,000 fatalities in 2019 [1], with the yearly diagnoses expected to reach 225,000 in. Cigarette smoke is one of the largest contributors to lung cancer diagnoses, but it has been established that a combination of lifestyle, genetic, and environmental components contributes to an individual’s risk and development of lung cancer [3]. Factors that put individuals at a greater risk for lung cancer include cigarette smoke, environmental pollutants, alcohol consumption, adverse dietary consideration, physical inactivity, and hereditary markers [3]. While treatments continue to improve, the prevalence and severity of lung cancer necessitates more refinement of treatment modalities
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