Long-Term Administration of Fibroblast Growth Factor 21 Prevents Chemically-Induced Hepatocarcinogenesis in Mice

In this study, we explored whether treatment with FGF-21 could prevent diethylnitrosamine (DEN) induced hepatocarcinogenesis in mice. Hepatoma was induced by injection of DEN every three days for 18 weeks. For the prophylactic experiment, mice were firstly injected with FGF-21 for 2 weeks, then FGF-21 was administered to the mice once daily in association with DEN injection till the end of the experiment. The hepatoma incidence of mice treated with FGF-21 was 13.3 %, while the incidence of mice treated with saline was 61.5 %. To understand the mechanisms, we compared the expression of beta klotho (KLB) and oxidative stress level in the livers between the mice treated with FGF-21 and saline. We found that FGF-21 could suppress DEN-induced oxidative stress and up-regulate the expression of KLB in the livers. To confirm these results, we compared the expression of KLB in L02 cells stimulated with or without FGF-21. Besides, we established DEN-induced oxidative stress cell model to affirm the relationship between FGF-21 and DEN-induced oxidative stress in vitro. Results showed that FGF-21 increased the expression of KLB and diminished the DEN-induced oxidative stress in vitro in a dose dependent manner. Systemic administration of FGF-21 can prevent DEN-induced hepatocarcinogenesis via suppressing oxidative stress and increasing the expression of KLB.