Fig. 6
Sorafenib/IL4-induced METs enhanced ferroptosis resistance of HCC cells. A CCK-8 assay and B transwell migration assay of Hepa1-6 and Hep3B cells (100 × magnification). n = 3. C The content of Fe2+ in Hepa1-6 and Hep3B cells, detected by the Iron Assay kit (Colorimetric). n = 6. D Detection of lipid peroxidation (lipid ROS) in Hepa1-6 and Hep3B cells with the mean fluorescence intensity (MFI) of BODIPY™ 581/591 C11 by flow cytometry. n = 3. E Western Blot assay of GPX4 protein expression level in Hepa1-6 and Hep3B cells. NC: HCC cells without treatment. Sora: HCC cells treated with sorafenib. DFO: HCC cells treated with deferoxamine (DFO). Sora + IL4: HCC cells were treated with sorafenib, and macrophages were treated with IL4. Sora + IL4 + PADI4-IN: HCC cells were treated with sorafenib, and macrophages were treated with IL4 and PADI4 inhibitor GSK484. Sora + IL4 + DNase I: HCC cells were treated with sorafenib, and macrophages were treated with IL4 and DNase I. Sora + DFO: HCC cells were treated with sorafenib and DFO. Sora + DFO + IL4: HCC cells were treated with sorafenib and DFO, and macrophages were treated with IL4. Sora + DFO + IL4 + PADI4-IN: HCC cells were treated with sorafenib and DFO, and macrophages were treated with IL4 and PADI4 inhibitor GSK484. Sora + DFO + IL4 + DNase I: HCC cells were treated with sorafenib and DFO, and macrophages were treated with IL4 and DNase I. Statistical significance was calculated by one-way analysis of variance (ANOVA) followed by Tukey’s multiple comparisons test (B-D). Data represent the mean ± standard deviation (SD) of ≥ three independent experiments. *, p < 0.05; **, p < 0.01; ***, p < 0.001