Fig. 4: Induction of hepatocytes senescence reduces the occurrence of HCC.

a Moderate chronic liver injury for 12 weeks (C 12w): Fah^−/− mice were given 2.5% NTBC for 12 weeks. Moderate chronic liver injury for 8 weeks, followed by severe acute liver injury for 4 weeks (C 8w + A 4w): Fah^−/− mice were given 2.5% NTBC for 8 weeks, and then treated with SALI for 4 weeks. Livers were collected at 12 weeks. b Graphs representing tumor incidence and tumor numbers in C 12w group and C 8w + A 4w group. The incidence of tumor in group C 8w + A 4w was significantly lower than that in group C 12w at 12 weeks. c–e Indicators of hepatocytes senescence were detected in livers of Fah^−/− mice after induction of SALI. Hepatocytes size was detected by H&E staining (c). p21 (d), SAHF (e), and Ki67 (f) staining were detected by immunohistochemistry. The bar graph on the right is a statistical chart of the corresponding positive cells. g Proteins of p53-p21 signaling pathway were analyzed by Western blot. The bar chart of quantitative analysis is on the right. Shows are mean ± S.D. **p < 0.01. *p < 0.05. Scale bar, 100 µm