ALOX5 promotes esophageal squamous cell carcinoma radiosensitization by ferroptosis

Abstract

ObjectiveTo investigate the role of lipid peroxidation and ferroptosis pathways in esophageal squamous cell carcinoma (SCC) and to provide some information for clinical treatment. MethodsIt is an experimental research. We detected the lipid peroxidation levels in esophageal SCC cells with or without ferrostatin-1 (Ferr-1), a ferroptosis inhibitor, by C11-BODIPY staining at irradiation doses ranging from 0 Gy to 6 Gy. Then, we investigated the effects of ionizing radiation (IR) and Ferr-1 on the clonogenic survival. The expression of lipoxygenase ALOX5 after IR in the presence or absence of Ferr-1 was examined by Western blot method. The expression of lipoxygenase ALOX5 was overexpressed or knocked down in esophageal SCC cells by RNA interference technique, respectively. Then changes in lipid peroxidation levels and clonogenic survival levels were detected again. ResultsThe data suggest that IR causes lipid peroxidation and ferroptotic death in esophageal SCC cells, and as part of the cell death response induced by IR. IR causes ferroptotic toxicity in part by increasing ALOX5. When the lipoxygenase ALOX5 was overexpressed, the level of death from lipid peroxidation and ferroptotic toxicity also increased. However, knockdown of the lipoxygenase ALOX5 suppressed IR-induced lipid peroxidation levels and ferroptotic toxicity in esophageal SCC cells. ConclusionWe found that IR causes lipid peroxidation and ferroptosis in esophageal SCC, while modulating the expression of ALOX5 could be used as a radiosensitizer for radiotherapy.