Abstract 1622: Possible role of visfatin in hepatoma progression and the effects of branched-chain amino acids on visfatin-induced proliferation in human hepatoma cells

Abstract

Abstract Obesity and related metabolic abnormalities, including adipocytokine dysbalance, are risk factors for hepatocellular carcinoma (HCC). Visfatin, an adipocytokine that is highly expressed in visceral fat, is suggested to play a role in the progression of human malignancies. Branched-chain amino acids (BCAA) reduces the incidence of HCC in obese patients with liver cirrhosis and prevents obesity-related liver carcinogenesis in mice. In this study, we investigated the possible role of visfatin on HCC progression and the effects of BCAA on visfatin-induced proliferation of HCC cells. In patients with HCC, serum visfatin levels were significantly correlated with stage progression and tumor enlargement. Visfatin preferentially stimulated the proliferation of HepG2, Hep3B, and HuH7 human HCC cells compared with Hc normal hepatocytes. Visfatin phosphorylated ERK, Akt, and GSK-3β proteins in HepG2 cells. LY294002 (a PI3K inhibitor), PD98059 (a MEK1 inhibitor), CHIR99021 (a GSK-3β inhibitor), and BCAA significantly inhibited visfatin-induced proliferation in HepG2 cells. BCAA also inhibited phosphorylation of GSK-3β, increased cellular levels of p21, caused cell cycle arrest in G0-G1, and induced apoptosis in HCC cells in the presence of visfatin. These findings suggest that visfatin plays a critical role in the proliferation of HCC cells and may be associated with the progression of this malignancy. In addition, BCAA might inhibit obesity-related liver carcinogenesis by targeting and, possibly, by overcoming the stimulatory effects of visfatin. 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 1622. doi:1538-7445.AM2012-1622