Obesity is associated with the development and progression of liver disease to hepatocellular carcinoma (HCC). Obesity is characterized not only by low-grade inflammation but elevated plasma concentrations of insulin and insulin-like growth factor 1 (IGF-1), visfatin, and resistin. Obesity and liver cancer promote physiological changes related to cellular proliferation, ROS, MMP section, invasion, and lipid accumulation. Adipokines, such as visfatin and resistin, have been shown to promote liver cancer incidence and progression. Studies have yet to determine the role of visfatin and resistin in an obesity-induced liver cancer phenotype. Our objective was to investigate the effect of neutralizing antibodies on OB and NW sera to determine the contribution of visfatin and resistin in obesity-induced invasive liver cancer phenotype.
Using an in vitro model, sera from obese (OB) or normal weight (NW) males (based on BMI) were used to determine the efficacy of neutralizing antibodies of visfatin and resistin in reducing an obesity-induced liver cancer phenotype. HepG2 and SNU-449 cells were exposed to 5% OB and NW serum ± neutralizing antibodies for visfatin or resistin.
The neutralizing resistin and visfatin antibodies suppressed obesity-induced growth, invasion, and MMP secretion in liver cancer cells. These physiological changes corresponded with a decrease in phosphorylated ERK and Akt along with CAP1 and β-catenin.
Collectively, visfatin and resistin play an important role in promoting an obesity-induced liver cancer phenotype by mediating proliferation, lipogenesis, ROS, MMP, and invasion.