Fig. 1. TRCs resist radiotherapy and chemotherapy by evading ferroptosis.
a,b, HONE1 TRCs and bulk cells were treated with radiation (IR, 8 Gy) with or without Fer-1 (1 µM) for 60 h. Fer-1 was added 6 h before IR treatment. The content of ferroptotic cell death signal PE (38:4)-OOH (a) and PE (40:4)-OOH (b) was measured by LC–MS/MS. P = 0.000028, 0.9999996, 0.000344 and 0.474506. c, Percentage of dead cells in TRCs and bulk tumor cells from HONE1 cells treated with IR in the absence or presence of Fer-1 (1 μM) and DFO (20 μM). P = 0.000000000000101. d, Percentage of dead cells in TRCs and bulk tumor cells from HK1 cells treated with IR in the absence or presence of Fer-1 (2 μM) and DFO (20 μM). P = 0.000000000000019. e–g, Dose-dependent toxicity of ferroptosis inducers RSL3 (e), FIN56 (f) or FINO2 (g) induced cell death of TRCs and bulk tumor cells (HONE1). n = 3 replicates from one representative of three independent experiments. h–j, Percentage of dead cells in TRCs and bulk tumor cells from HONE1 cells treated with indicated inhibitors and RSL3 (15 μM) (h), FIN56 (10 μM) (i) or FINO2 (10 μM) (j). Fer-1, 1 μM; Z-VAD (Z-VAD-FMK), 10 μM and Nec-1 (necrostatin-1), 2 μM. P = 0.000000000042792, 0.000000000075223 and 0.000000002261459. k, Accumulation of RSL3-induced oxygenated PE that contains AA (C20:4) or AdA (C22:4) in TRCs and bulk tumor cells from HONE1 cells. P = 0.00000879. n = 3 replicates from one representative of three independent experiments. Data are shown as mean ± s.d.; one-way ANOVA (a,b,k) or two-way ANOVA (c,d,h–j). n = 3 independent experiments. NS, not significant.