黄连碱靶向铁死亡逆转鼻咽癌放疗抵抗的研究进展OA

Radiotherapy resistance in nasopharyngeal carcinoma(NPC)is a major cause of treatment failure in patients with locally advanced disease.The core mechanism involves the escaping of tumor cells from ferroptosis through aberrant activation of the System Xc-/GSH/GPX4 antioxidant axis and the Nrf2 pathway.Coptisine,a natural isoquinoline alkaloid,effectively dismantles the ferroptosis defense barrier through multi-target interventions,including downregulating SLC7A11 expression,depleting glutathione,promoting GPX4 degradation,and inhibiting Nrf2 nuclear translocation.Furthermore,coptisine exerts a synergistic lethal effect with radiotherapy-induced reactive oxygen species,significantly reversing the radioresistant phenotype.However,coptisine has pharmaco-kinetic limitations such as poor water solubility and low bioavailability.Nanodelivery systems(e.g.,liposomes,magnetic nanocarri-ers)offer new strategies for its clinical translation.Screening for biomarkers such as SLC7A11 and GPX4 will facilitate individualized precision medicine.This article systematically reviews the molecular mechanisms and clinical translation prospects of coptisine targe-ting ferroptosis to reverse radiotherapy resistance in nasopharyngeal carcinoma,providing a theoretical basis for developing novel radio-sensitizing agents.