Fig. 8

Therapeutic efficacy of anti-AREG and FK866 in the CEA-SV40 mouse model of EGC. a Schematic flowchart outlining the induction of EGC in CEA-SV40 mice and the oral administration protocol for anti-AREG, FK866, and the combination treatment (anti-AREG + FK866). b Representative images of mouse stomachs dissected longitudinally to expose the gastric mucosa for macroscopic examination. c Macroscopic examination of early lesions revealed no visible abnormalities in all groups. However, H&E staining identified distinct histological features: deep nuclear staining and polarity alterations were prominent in the untreated CEA-SV40 group, while the anti-AREG group exhibited mild dysplasia, and the FK866 and combined treatment groups showed the least dysplasia. 200 μm. d Probability of precancerous lesion formation (%) across groups. The untreated CEA-SV40 mice showed the highest incidence (~100%), while anti-AREG and FK866 treatments significantly reduced lesion probability. The combined treatment group demonstrated an approximately 50% reduction, comparable to individual treatments. e Immunohistochemical staining scores for “initiation-promoting” gene-set, NFκB, JAK/STAT, and MAPK pathways showed distinct expression patterns across groups. f Representative IHC staining images for PMC_2 markers (ITGA2), fibroblast marker (Vimentin) along with key pathway markers (pp38, p-STAT1 and pp65) revealed significant differences among groups. g Western blot analysis of PD-L1, STAT, p-STAT1, p38, p-p38, p65, and p-p65 after 72-h treatments in Pre-EGC, Pre-EGC + 200 ng/ml AREG, and Pre-EGC + fibroblasts groups treated with 100 ng/ml NAMPT/200 ng/ml AREG. *p < 0.05, **p < 0.01, ***p < 0.01