The effect of Exercise and Vitamin D3 Supplementation on Tumorigenesis and Pulmonary Function in a Lung Tumor Animal Model
Authors: Williams Brian T , Hershberger Pamela A , Personius Kirkwood E , Ray Andrew D 
Published: November 2023

BackgroundLung cancer is a leading cause of cancer related death in the United States. Other than smoking cessation, no primary prevention strategies are available to reduce lung cancer risk. Vitamin D and exercise represent two safe and inexpensive prevention strategies that may interact to reduce lung cancer‐related risk, tumorigenesis and muscle dysfunction.PurposeTo establish the effects of vitamin D3 (Vit D3) supplementation alone and in combination with exercise on lung tumorigenesis, diaphragm muscle strength and the hypercapnic ventilatory response (HVR) in A/J mice.Methods60 female A/J mice were randomized to receive 1 of 2 diets that differ only in Vit D3 content (25 IU VD3/kg (Low D3) or 10,000 IU VD3/kg (High D3)). Mice in each diet group were further randomized into an exercise (voluntary wheel running) or sedentary control group. After 6 weeks of diet and exercise acclimatization, mice received the tobacco carcinogen, NNK. Lung tumorigenesis, diaphragm in‐vitro contractile properties, and the HVR (7 % CO2, 26% O2) ventilatory response were measured 14 weeks later.ResultsTumorigenesis: Lung tumor area was 8.6% smaller in the exercising mice vs control mice (P<0.05), and 14.1% smaller in exercising Low D3 vs sedentary Low D3 mice (P<0.05). Tumor perimeter (P=0.06) and tumor radius (P=0.08) were 4.1% and 3.9% smaller in the exercising vs control mice.Contractile PropertiesDiaphragm muscle force generation was 17% higher (P<0.05) in the exercising Low D3 mice vs the sedentary Low D3 mice.VentilationOverall, minute ventilation in exercising mice was 9.2% lower in room air compared to sedentary controls (P=0.1). The reduction was due to a 9.7% lower tidal volume (Tv) (P=0.05). High D3 mice had a 14.9% lower minute ventilation in room air (P=0.03) compared to the Low D3 mice. The reduction was due to a 15.3% lower Tv (P=0.03) in room air. Minute ventilation in exercising mice was 8.5% lower during HVR compared to sedentary mice (P=0.08). The reduction was due to a 7% lower Tv (P=0.1). Minute ventilation in High D3 mice was 8% lower during HVR compared to Low D3 mice (P=0.1). The reduction was due to a 9.7% lower Tv (P=0.05).Body WeightExercising Low D3 mice (21.1±0.5g) weighed less than sedentary Low D3 mice (23.3±0.5g) (P<0.05). Exercising High D3 mice (19.9±0.4g) weighed less than sedentary High D3 mice (22.5±0.4g), (P<0.05) and was the lowest of all the groups.ConclusionExercise and Vit D3 intake may play a role in tumorigenesis, force generation and ventilation in the NNK model of lung cancer. Exercise has the potential to reduce tumorigenesis and have a protective effect on diaphragm muscle strength. A high Vit D3 diet could lead to lower ventilation due to a lower tidal volume at rest and during a 7% hypercapnic challenge. Exercise also led to reduced ventilation due to a reduced tidal volume. The reduced tidal volumes may be due to the lower body weight of the exercising and high Vit D3 diet mice. These results show the potential therapeutic benefits of exercise and Vit D3 in a murine lung cancer model.