Caloric Restriction Ketogenic Diets (KR) Enhance Radiotherapy Responses in Lung Cancer Xenografts

Abstract

<h3>Purpose/Objective(s)</h3> Dietary interventions can change metabolite levels in the tumor microenvironment, which might then affect cancer cell metabolism to alter tumor growth. Caloric restriction (CR) and ketogenic diet (KD) are often thought to limit tumor progression. <h3>Materials/Methods</h3> Mice bearing Lewis Lung Carcinoma xenografts were randomly divided into ad libitum diet group (AL), radiation group (RT), KR diet group (KR), or KR + RT group (KT). Mice in KR and KT group were fed a KR (KetoCal 4:1 fats: proteins+carbohydrates; 70% of total energy). Mice in RT and KT group were treated with radiation (4Gy*3f). Mice weights, tumor size, blood ketone levels and survival were monitored. <h3>Results</h3> Blood ketone levels were significantly higher for the mice consuming a KR diet compared to standard diet (3.2 mmol/L vs 0.8 mmol/L at week 3, P < .001). Some mice with KR diet lost a significant amount of weight (10%ཞ15% of starting weight) by the end of the treatment. The KR diets combined with radiation resulted in slower tumor growth in Lewis Lung Carcinoma xenografts and longer survival time (P < 0.05), relative to radiation alone. The KR diet also slowed tumor growth and prolonged survival (P < 0.05), relative to control. Hematological and pathological examinations indicated that the KR diet was safe and well tolerated, and no significant cardiac, hepatic and renal toxicity was observed. <h3>Conclusion</h3> Blood ketone levels were significantly higher for the mice consuming a KR diet compared to standard diet (3.2 mmol/L vs 0.8 mmol/L at week 3, P < .001). Some mice with KR diet lost a significant amount of weight (10%ཞ15% of starting weight) by the end of the treatment. The KR diets combined with radiation resulted in slower tumor growth in Lewis Lung Carcinoma xenografts and longer survival time (P < 0.05), relative to radiation alone. The KR diet also slowed tumor growth and prolonged survival (P < 0.05), relative to control. Hematological and pathological examinations indicated that the KR diet was safe and well tolerated, and no significant cardiac, hepatic and renal toxicity was observed.