Inhibition of Diethylnitrosamine-Induced Hepatocarcinogenesis in Mice by a High Dietary Protein Intake

Abstract

Epidemiological and experimental evidence supports the key role of diet in the development of many types of cancer. Recent studies have suggested that dietary modifications may be beneficial for individuals at high risk for hepatocellular carcinoma (HCC). In this study, we investigated the effect of a high-protein (HP; 20% casein) dietondiethylnitrosamine (DEN)-induced hepatocarcinogenesis. Mice were given free access to water with 30 μg/ml DEN and fed a normal or HP diet for 22 wk. The results showed mice consuming HP diets had reduced mortality rates and body weights and lower hepatic enzyme activity compared to DEN-treated mice on a normal diet. HP consumption also promoted collagen accumulation in the liver, and reduced numbers of proliferating hepatocytes and infiltrating inflammatory cells, as well as decreased expression of inflammatory factor interleukin-1β, and nuclear factor κB activation. These data indicate that HP diets can inhibit DEN-induced hepatocarcinogenesis via suppression of the inflammatory response and provide a new evidence for the dietary management of clinical patients with hepatocellular carcinoma.

ACKNOWLEDGMENT

Qiyang Shou and Fangming Chen contributed equally to this article.

FUNDING

The work was supported by Province Natural Science Foundation of Zhejiang (Grant LY13H280005 to Huiying Fu and Grant LY13H280006 to Jianchao Wang), Zhejiang Provincial TCM Sci-research Foundation Plan (Grant 2014ZQ013 to Huiying Fu), National Science Foundation of China (Grant 81202972 to Qiyang Shou, and Grant 81001667 to Huiying Fu) and Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health talents.