Figure 11

WNK1–OSR1 axis inhibitors combined with oligo-fucoidan attenuate HCC proliferation. (a) The treatment scheme of WNK1 and OSR1 inhibitors combined with oligo-fucoidan in [HBx,src,p53^−/−,RPIA] HCC transgenic fish. The expression of proliferation markers (b) ccne1, (c) cdk1, and (d) cdk2 in various combinations of drug-treated 5-month-old [HBx,src,p53^−/−,RPIA] (HSPR) transgenic fish compared to WT. Rego: Regorafenib, Rafox: Rafoxanide as OSR1 inhibitor; WNK463 as WNK1 inhibitor; OF: oligo-fucoidan. The quantification of the histopathological features derives from H&E stain: (e) mitotic figures, (f) trinucleated hepatocytes, (g) karyomegalic cells in various combinations of drug-treated 5-month-old [HBx,src,p53^−/−,RPIA] transgenic fish compared to WT. (h) The expression of cell senescence marker il1β in various combinations of drug-treated 5-month-old [HBx,src,p53^−/−,RPIA] (HSPR) transgenic fish compared to WT. We performed three replicates, and for each qPCR, there are triplicates for each sample. Five adult fish are included in each experiment. One-way ANOVA analysis followed by multiple analysis of variance was used to identify the statistical significance between groups. *: p ≦ 0.05; **: p ≦ 0.01; ***: p ≦ 0.001; ****: p ≦ 0.0001; ns: no-significance.