胶质母细胞瘤脂肪酸代谢与化疗耐药性关系的研究进展  

Progress in the study of the relationship between fatty acid metabolism and chemotherapy resistance in glioblastoma

作　　者：许林宗 孙晓琳[1] 张展昱 李晓梅[1] Xu Linzong;Sun Xiaolin;Zhang Zhanyu;Li Xiaomei(Tumor Research and Therapy Center,Shandong Provincial Hospital,Shandong University,Jinan 250021,Shandong,China)

机构地区：[1]山东大学,山东省立医院肿瘤治疗中心,济南250021

出　　处：《肿瘤代谢与营养电子杂志》2022年第4期530-535,共6页Electronic Journal of Metabolism and Nutrition of Cancer

摘　　要：细胞在癌变的过程中代谢模式会发生显著变化,涉及糖、脂质、氨基酸和核酸代谢等方面。正是由于这些重要代谢途径的异常激活和重新编程,赋予癌细胞无限增殖潜能和恶性生物学特征。胶质母细胞瘤的代谢重编程也是肿瘤发生发展过程中的显著特征之一,其中脂肪酸代谢在能量储存、细胞增殖、重要信号分子合成及化疗耐药方面发挥着重要作用。目前胶质母细胞瘤的治疗仍然面临巨大挑战,对标准治疗药物替莫唑胺产生耐药性是治疗难点之一。与初发胶质母细胞瘤细胞相比,化疗耐药的胶质母细胞瘤细胞表现出更加活跃的脂肪酸代谢能力。伴随肿瘤相关代谢重编程的细胞内外代谢物的改变,对基因表达、细胞分化和肿瘤微环境具有深远的影响。化疗耐药的胶质母细胞瘤细胞的脂肪酸代谢关键酶及调节因子上调,脂肪酸外源性摄取、从头合成及氧化能力增强,在治疗应激时为细胞提供主要的能量支持。因此,靶向胶质母细胞瘤脂肪酸代谢途径可能成为攻克胶质母细胞瘤化疗耐药的新策略。Cancer cells undergo significant changes in metabolic patterns during carcinogenesis,involving many aspects of sugar,lipid,amino acid and nucleic acid metabolism.It is the abnormal activation and reprogramming of these important metabolic pathways that endow cancer cells with unlimited proliferative potential and malignant biological features.Metabolic reprogramming in glioblastoma is also one of the distinctive features of tumorigenesis,in which fatty acid metabolism also plays an important role in energy storage,cell proliferation,synthesis of important signaling molecules,and chemoresistance.The treatment of glioblastoma still faces great challenges,and resistance to the standard therapeutic agent temozolomide is one of the treatment difficulties.Chemoresistant glioblastoma cells exhibit more active levels of fatty acid metabolism compared to primary glioblastoma cells.Alterations in intra-and extracellular metabolites that accompany cancer-associated metabolic reprogramming have profound effects on gene expression,cellular differentiation and tumor microenvironment.Chemoresistant glioblastoma cells have upregulated key enzymes and regulators of fatty acid metabolism,with enhanced exogenous uptake,de novo synthesis and oxidation of fatty acids,providing major energy support for cells during therapeutic stress.Therefore,targeting glioblastoma fatty acid metabolic pathways may be a new strategy to overcome chemoresistance in glioblastoma.

关 键 词：胶质母细胞瘤 脂肪酸代谢 化疗抗性 

分 类 号：R739.4[医药卫生—肿瘤]