Fig. 7: Targeting DCAF7 or USP2 sensitizes HCC cells to sorafenib by inducing ferroptosis.

A and B The relative cell viability of the shNC and shDCAF7-HCC cells treated with different concentrations of sorafenib for 24 h. Mean ± SD (n = 3, biological replicates). C Schematic representation of the treatment schedule of sorafenib and Fer-1 for shNC or shDCAF7 Huh7 xenografted mice. D–G Images (D), growth curves (E), tumor weight (F), and MDA (G) of the shNC or shDCAF7-expressing Huh7 xenografted mice treated as indicated. Mean ± SD (n = 6 mice per group). H and I The relative viability of HCC cells treated with the indicated concentrations of ML364 and sorafenib for 24 h. Mean ± SD (n = 3, biological replicates). J and K The relative viability of HCC cells treated with the indicated concentrations of ML364 and sorafenib (20 μM for Huh7, 10 μM for SNU-449) in the absence or presence of Fer-1 (1 μM) for 24 h. Mean ± SD (n = 3, biological replicates). L and M The OD₄₅₀ of the HCC cells treated with ML364 (2 μM), sorafenib (2 μM), or the combination treatment of sorafenib (2 μM) and ML364 (2 μM) for different durations. Mean ± SD (n = 3, biological replicates). N Schematic representation of the therapy schedule of sorafenib, ML364, or combination therapy for Huh7 xenografted mice. O–R Images (O), growth curves (P), tumor weight (Q), and MDA (R) of the Huh7 xenografted mice treated as indicated. Mean ± SD (n = 6 mice per group). The P-values were calculated using one-way ANOVA analysis with a Tukey’s multiple comparisons post hoc test (F–K, Q, and R), and two-way ANOVA analysis with a Sidak’s multiple comparisons post hoc test (A, B, E, L, M, and P). NS, P > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.