Fig. 7.

Punicalin is a potential PSTK inhibitor that synergizes with Sorafenib in vitro and in vivo. A Schematic overview of the high throughout virtual screening approach used for PSTK inhibitor identification. B Docking scores for the top 10 potential PSTK inhibitors. C Punicalin binds to the active pocket of PSTK through six H-bonds formed with Lys200, Asp41, Asp79, Thr80, Tyr82, and Met86. D Geraniin and Punicalin exhibited significant anti-HCC activities by CCK-8 assay (n=6). E-F Punicalin/Geraniin treatment for 48 h significantly downregulates PSTK and GPX4 at the protein level. G Changes in tumor volumes over time for mice implanted with Hep3B cells and treated with Sorafenib with or without Punicalin/Geraniin. H-J Measures of tumor volume and tumor weight values of mice at the study endpoint. K Representative images (six random visual fields) of GPX4, PSTK and Ki-67 staining in tumor samples from the Punicalin/Geraniin/Vehicle treatment groups and immunohistochemical scores (n=6). Scale bar: 100 μm. L Changes in murine body weights over time. M Representative images (six random visual fields) of H&E staining of intestine, lung, liver, and kidney samples from Punicalin/Geraniin/Vehicle treated mice. Scale bar: 100 μm. *p<0.05; **p<0.01; ***p<0.001; Student’s t-test