Sorafenib-resistant HCC cells show higher ERRγ expression and are less sensitive to sorafenib-induced ferroptosis. (A) Sorafenib-sensitive (SS) and -resistant (SR) HCC (Huh7 and SK-Hep1) cells were treated with the indicated concentrations of sorafenib for 24 h and cell viability was assayed using the CCK-8 assay. (B) Representative images of C11-BODIPY, a marker of lipid peroxidation, in sorafenib-resistant (SR) HCC cells, and in parental cells (SS) treated with sorafenib (left panel). Quantification of C11-BODIPY fluorescence in cells (right panel). (C) Relative expression of ERRγ mRNA in sorafenib-resistant HCC cells (data from the GEO database). (D) Relative expression of ERRγ mRNA levels in sorafenib-sensitive (SS) and -resistant (SR) HCC cells. (E) Representative western blot analysis of ERRγ protein levels in sorafenib-sensitive (SS) and -resistant (SR) HCC cells. Data in the bar graph are mean ± SEM of three independent experiments. N.S., not significant; *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. Sora, Sorafenib.