Research Paper Volume 15, Issue 20 pp 11033—11051

Figure 5. The oncogenic activity of SSH1 is mediated by circadian rhythm disruption, in vivo (A) Workflow schema of the orthotopic HCC mice model generation. (B) Photo-image showing the differential effect of SenAlight and SenAdark on the tumor sizes in xenografted mice. Line graphs showing the differential effects of SenAlight and SenAdark on the (C) average tumor volume in and (D) body weight of the treated mice compared with the PBS control mice, at the indicated time-points. (E) Histograms showing how PBS, SenAlight and SenAdark affect the number of intrahepatic and lung metastasis nodules. (F) Representative western blot images of the effect of PBS, SenAlight and SenAdark on the expression levels of SSH1, CLOCK, BMAL1, CRY1, and β-catenin in dissociated HCC cells from tumors extracted from xenografted mice. GAPDH served as a loading control. (G) Representative tissue staining images showing the effect of PBS, SenAlight and SenAdark on the staining intensity and distribution of SSH1, CLOCK, BMAL1, and CRY1 proteins in tumors extracted from xenografted mice. (H) a pictorial description of the mechanism of regulation of HCC progression via SSH1-β-catenin and WNT signaling. The data are presented as the mean ± standard error of mean (SEM), n = 5/group.