Fig. 4: High GPX4 expression promotes chemotherapy resistance in NPC cells and is correlated with poor survival in NPC patients.

A. Cell death of EBV-negative and EBV-positive NPC cells was determined by flow cytometry after treatment with cisplatin (DPP) with or without the caspase inhibitor VAD-FAK or PBS (control) (n = 3). B Lipid ROS production in the indicated cells was determined by flow cytometry after treatment with DDP, paclitaxel (TAX), or PBS (control) (n = 3). C Representative immunoblots of GPX4 in EBV-positive CNE2 and HK1 cells with stable knockdown of endogenous GPX4. D Thirty hours after cystine starvation, cell death was assessed by SYTOX Orange staining. E Dose–response curve for DPP, 5-fluorouracil (5-FU), and TAX treatment with or without the GPX4 inhibitor RSL3 for 48 h in the indicated cells (n = 4). F. Subcutaneous tumors formed by EBV-negative and EBV-positive CNE2 cells in nude mice were excised 17 days after inoculation. DDP (4 mg/kg) or RSL3 (10 mg/kg) was administered 4 days post inoculation. G, H. Growth curve and weight of xenograft tumors (n = 7). I TUNEL staining (red signal) assessing cell death in xenograft tumors. Scale bar, 50 µm. J Kaplan–Meier analysis of overall survival (OS) based on GPX4 expression in 181 NPC patients. Data are shown as the mean ± SD. **p < 0.01; ***p < 0.001. A and B, two-tailed unpaired t test. H two-tailed Mann–Whitney test. D scale bar: 100 µm.