Fig. 2

Hepatic NOD2 deficiency suppresses DEN/CCl₄-induced hepatocarcinogenesis. a Effect of hepatic NOD2 deficiency on tumor growth in DEN/CCl₄-induced HCC model. Male mice were injected with DEN (25 mg/kg, i.p.) at the age of 14–16 days followed by 8 injections of CCl₄ (1.2 ml/kg, i.p., biweekly, starting 4 weeks after DEN injection) and killed 8 months after DEN injection. Representative gross appearance of the livers. Arrowheads indicate tumors in liver. b Quantification of tumor incidence in Nod2^f/f (n = 15) and Nod2^△hep (n = 15) mice (left panel). Quantification of tumor number (middle panel) and tumor size (right panel) in Nod2^f/f (n = 15) and Nod2^△hep (n = 11) mice. c Representative H&E staining of liver sections from Nod2^f/f and Nod2^△hep. Scale bar, 200 μm (top panel) or 25 μm (bottom panel). d Survival rate of mice treated with DEN/CCl₄. Median survival time for Nod2^f/f (n = 20) and Nod2^△hep (n = 20) mice was 330 and 399 days, respectively. e–f TUNEL (e) and Ki67 staining (f) in Nod2^f/f and Nod2^△hep mice livers. Arrowheads indicate Ki67-positive cells, n = 5–6. Scale bar, 100 μm (top panel) or 50 μm (bottom panel). g Serum ALT and AST levels in Nod2^f/f and Nod2^△hep mice. n = 6. h Sirius red and Masson staining in Nod2^f/f and Nod2^△hep mice livers 4 months after DEN injection. n = 6. Scale bar, 100 μm. Data were shown as mean ± SD, and significance was determined using ordinary one-way ANOVA with Sidak test (e, f), and unpaired Student’s t test (b, g, h). *P < 0.05, **P < 0.01