The COX-2 Inhibitor Celecoxib Sensitizes Nasopharyngeal Carcinoma Cells to Ferroptosis

Background:: Nasopharyngeal cancer [NPC] is prevalent in Southeast Asia and North Africa, and is generally associated with limited treatment options and poor patient prognosis. Objective:: Ferroptosis is a recently observed cell death modality and has been shown to link to the efficacy of different anti-cancer treatments, thus offering opportunities for the develop-ment of novel therapies. This study aims to investigate the potentiating effects of COX-2 in-hibitors on ferroptosis in nasopharyngeal cancer. Methods:: The inhibitory effects of COX-2 inhibitors celecoxib and rofecoxib on nasopharyn-geal cancer cells were assessed with MTT, colony formation, sphere formation, Transwell, and wound healing assays. The status of COX-2 with celecoxib and rofecoxib treatment was investigated by Western blotting and immunofluorescence experiments. Ferroptosis was in-duced with the GPX4 inhibitor RSL3 with or without COX-2 inhibition and was monitored by fluorescence microscopy. Transcriptomic profiling was conducted with 5-8F cells treated with DMSO as control or celecoxib, and ferroptosis-related candidates were validated by RT-PCR analysis. Results:: Celecoxib and rofecoxib effectively inhibited the growth and migration of nasopha-ryngeal cancer cells. Both inhibitors evidently sensitized nasopharyngeal cancer cells to fer-roptosis induction by RSL3, with celecoxib outperforming rofecoxib. Celecoxib treatment re-sulted in significantly differentially expressed genes in 5-8F cells, among which CHAC1 was validated as a ferroptosis-related target. Conclusion:: The COX-2 inhibitor celecoxib effectively sensitized nasopharyngeal cancer cells to ferroptosis induction.