Figure 7.
DDK inhibitor XL413 enhances the therapeutic effects of anti-PD-1 immunotherapy. (a-e). Hepa1‐6 cells were inoculated into the liver of C57BL/6J mice to establish HCC orthoptic xenograft model (n = 5 for each group). The models were treated with XL413 (50 mg/kg, oral gavage, 6 days per week) or PBS for two weeks. Tumor appearance (a), tumor volume (b) and weight (c), and survival of mice (d). Expression of p-STAT3-Y705 in tumor tissue was detected by IHC staining (e). Scale bars: 20 μm (400× magnification). (f-i). The combination of XL413 (50mg/kg, oral gavage, 6 days per week) and anti-PD-1 antibody treatment (200μg, intraperitoneally administrated, every three days) in orthotopic HCC mouse models. (f). Representative images of Hepa1-6 tumors from each group (per group, n=6). Qualification of tumor volume (g) and weight (h). Survival of mouse xenograft models (i). IHC staining were applied in separated tumors from orthotopic HCC mouse model (j). Scale bars: 50 μm for 200× magnification and 20 μm for 400× magnification. (k). Schematic diagram for the regulatory relationship among p65, DBF4, CDC7, XPO1 and STAT3 in HCC cells. * P <0.05, ** P < 0.01, ***P < 0.001, ****P < 0.0001; ns, not significant.