Fig. 4|. Targeting 7-DHC biosynthesis regulates cancer cell sensitivity to ferroptosis.

a, Schema of cholesterol biosynthesis pathway. TASIN-30 is an inhibitor of EBP. b, Heat map (data summarized from Extended Data Fig. 8b) depicting the dose-dependent toxicity of RSL3 in various human cancer cell lines (human kidney cancer cell line 786-O; human osteosarcoma cell line U2OS; human breast cancer cell line MDA-MB-231; human colon cancer cell line DLD1; human hepatocellular carcinoma cell lines HepG2, Hep3B, HuH-7, PLC/PRF/5 and SK-Hep1), TASIN-30 treatment vs. the DMSO control (Ctrl). c, The fitness scores of SC5D and DHCR7 in 810 cancer cell lines were explored by Project Score Database. Fitness score is a quantitative evaluation of the cell viability effect elicited by CRISPR-Cas9-mediated cell inactivation. d, Cell viability of SU-DHL-8 cells treated with indicated concentrations of TASIN-30 for 24 h after pretreatment of Fer-1 (1 μM), DFO (5 μM) or Idebenone (5 μM). e, Lipid peroxidation assessment of SU-DHL-8 cells treated with indicated concentrations of TASIN-30 for 16 h with pretreatment of Fer-1 (1 μM). f, Levels of 7-DHC in SU-DHL-8 cells treated with TASIN-30 (3 μM) for 24 h, both cells were cultured with Fer-1 (1 μM). g, Tumour growth rates of SU-DHL-8 xenografts with indicated treatments over time. n=7 in each group. h, Quantification of immunohistochemical 4-HNE staining in SU-DHL-8 xenografts with indicated treatments. n=7 in each group. Data are representative of three (b, d, e) and two (f, g) independent experiments. For d-f, data are mean ± s.d. of n=3 biological replicates, statistical analysis was performed one-way ANOVA (e and f). For g, h, data plotted are mean ± s.e.m., statistical analysis was performed two-way ANOVA (g and h) ;*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.