铁死亡抵抗分子FSP1介导的食管癌5-氟尿嘧啶耐药机制及iFSP1化疗增敏作用的探究OA

Objective To investigate the expression of ferroptosis suppressor protein 1(FSP1)in esophageal cancer,its relationship with prognosis,the mechanism by which it mediates 5-fluorouracil(5-FU)chemotherapy resistance,and the chemosensitizing effect of the FSP1 inhibitor(iFSP1).Methods The Cancer Genome Atlas(TCGA)was used to analyze FSP1 expression and its prognostic significance in esophageal cancer.Immunohistochemistry was performed to detect FSP1 expression in esophageal cancer and adjacent non-cancerous tissues.A 5-FU resistant esophageal cancer cell line was established using the concentration gradient method.Western blot was used to detect FSP1 protein expression in the resistant cells.Cell immunofluorescence,flow cytometry,CCK-8 assay,and colony formation assay were employed to evaluate the reversal effect of iFSP1 on chemoresistance in esophageal cancer.Results FSP1 was highly expressed in esophageal cancer tissues and was associated with poor prognosis.FSP1 protein expression was increased in 5-FU resistant esophageal cancer cells.High FSP1 expression was closely correlated with resistance to 5-FU chemotherapy.Treatment with a specific FSP1 inhibitor enhanced ferroptosis in tumor cells and increased the sensitivity of esophageal cancer cells to 5-FU.Conclusion FSP1 mediates 5-FU chemotherapy resistance in esophageal cancer by inhibiting ferroptosis in tumor cells.Targeting FSP1 may reverse chemotherapy resistance in esophageal cancer.