恶性肿瘤可通过多种细胞机制,产生对抗癌药物和放疗的抗性,即所谓耐药现象。细胞自噬是肿瘤细胞耐药的一个重要原因。高迁移率族蛋白B-1(HMGB1)是高度保守的非组蛋白DNA结合蛋白,在DNA结构、基因转录、基因重组、DNA损伤修复以及细胞存活等方面发挥重要的调控作用;HMGB1在细胞内的功能,与其氧化还原状态和细胞定位息息相关;在应激条件下,可从核内转位至胞质,启动细胞自噬,介导肿瘤细胞对抗癌药物和放疗的抗性。因此,HMGB1是克服肿瘤细胞耐药的潜在靶标。
Resistance to chemical drugs and irradiation therapy,namely,drug resistance are usually induced in malignant tumors through diverse mechanisms.An important mechanism is drug-induced autophagy.High-mobility group box-1 protein 1(HMGB1) is a highly conserved non-histone and DNA-binding protein that plays a key role in chromatin construction,gene transcription,recombination,DNA damage repair and cell death/survival etc.These functions of HMGB1 are related to its redox state and cellular localization.Upon cellular stresses,HMGB1 is translocated from nucleus to cytosol and induces autophagy,which eventually mediates cellular resistance to anti-cancer drugs and irradiation therapies.Thus,HMGB1 is becoming a potential target in tumor cells for overcoming drug resistance.