Abstract
Abstract Background and aims: Obesity and related metabolic abnormalities, including insulin resistance and a state of chronic inflammation, increase the risk of hepatocellular carcinoma (HCC). Abnormal activation of the IGF/IGF-1R axis is also involved in obesity-related liver tumorigenesis. In the present study, we examined the effects of (-)-epigallocatechin gallate (EGCG), a major biologically active component of green tea, on the development of diethylnitrosamine (DEN)-induced liver tumorigenesis in C57BL/KsJ-db/db (db/db) obese mice. Methods: Male db/db mice were given tap water containing 40 ppm DEN for 2 weeks and then they received drinking water containing 0.1% EGCG for 34 weeks. Results: At sacrifice, drinking water with EGCG significantly inhibited the development of liver cell adenomas in comparison to the control EGCG-untreated group. EGCG inhibited the phosphorylation of the IGF-1R, ERK, Akt, GSK-3β, Stat3, and JNK proteins in the livers of experimental mice. The serum levels of insulin, IGF-1, IGF-2, free fatty acid, and TNF-α were all decreased by drinking EGCG. EGCG also decreased the expression of TNF-α, IL-6, IL-1α, and IL-18 mRNAs in the livers. In addition, EGCG improved liver steatosis and activated the AMPK protein in the liver. Conclusion: EGCG prevents obesity-related liver tumorigenesis by inhibiting the IGF/IGF-1R axis, improving hyperinsulinemia, and attenuating chronic inflammation. EGCG, therefore, may be useful in the chemoprevention of liver tumorigenesis in obese individuals. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1616. doi:1538-7445.AM2012-1616
Published Version
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