Fig. 5. The NUPR1–LCN2 pathway limits ferroptotic cancer cell death in vivo.

a Athymic nude mice were injected subcutaneously with indicated PDHA1-knockdown (NUPR1^KD) or LCN2-knockdown (LCN2^KD) PANC1 cells for 7 days and then treated with IKE (40 mg/kg, i.p., once every other day) in the absence or presence of liproxstatin-1 (10 mg/kg, i.p., once every other day) at day 7 for 2 weeks. Tumor volumes were calculated weekly (n = 5 mice/group; two way ANOVA with Tukey’s multiple comparisons test on all pairwise combinations). b–e In parallel, the levels of Fe²⁺ (b), MDA (c), or PTGS2 mRNA (d) in isolated tumors and serum HMGB1 (e) at day 14 after treatment were assayed (n = 5 mice/group; one-way ANOVA with Tukey’s multiple comparisons test on all pairwise combinations). f Athymic nude mice were injected subcutaneously with PANC1 or MIAPaCa2 cells for 7 days and then treated with IKE (40 mg/kg, i.p., once every other day) in the absence or presence of ZZW-115 (5 mg/kg, i.p., once every other day) or liproxstatin-1 (10 mg/kg, i.p., once every other day) at day 7 for 2 weeks. Tumor volumes were calculated weekly (n = 5 mice/group; two-way ANOVA with Tukey’s multiple comparisons test on all pairwise combinations). g Indicated mPDAC cells were treated with erastin (10 µM) or RSL3 (1 µM) in the absence or presence ZZW-115 (2 µM) for 24 h and then cell death was assayed (n = 3 well/group, two-way ANOVA with Tukey’s multiple comparisons test on all pairwise combinations). ns: not significant. Data in a–e and g are presented as mean ± SD. The results in a–g are representative of those from 2 to 3 independent experiments.