Chen Xun, Chen Shangwu, Yu Dongsheng
Guangdong Provincial Key Laboratory of Stomatology, Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.
Guangdong Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
Metabolites. 2020 Jul 16;10(7):289. doi: 10.3390/metabo10070289.
Metabolic reprogramming is one of the hallmarks of tumors. Alterations of cellular metabolism not only contribute to tumor development, but also mediate the resistance of tumor cells to antitumor drugs. The metabolic response of tumor cells to various chemotherapy drugs can be analyzed by metabolomics. Although cancer cells have experienced metabolic reprogramming, the metabolism of drug resistant cancer cells has been further modified. Metabolic adaptations of drug resistant cells to chemotherapeutics involve redox, lipid metabolism, bioenergetics, glycolysis, polyamine synthesis and so on. The proposed metabolic mechanisms of drug resistance include the increase of glucose and glutamine demand, active pathways of glutaminolysis and glycolysis, promotion of NADPH from the pentose phosphate pathway, adaptive mitochondrial reprogramming, activation of fatty acid oxidation, and up-regulation of ornithine decarboxylase for polyamine production. Several genes are associated with metabolic reprogramming and drug resistance. Intervening regulatory points described above or targeting key genes in several important metabolic pathways may restore cell sensitivity to chemotherapy. This paper reviews the metabolic changes of tumor cells during the development of chemoresistance and discusses the potential of reversing chemoresistance by metabolic regulation.
代谢重编程是肿瘤的特征之一。细胞代谢的改变不仅有助于肿瘤的发展，还介导肿瘤细胞对抗肿瘤药物的耐药性。肿瘤细胞对各种化疗药物的代谢反应可以通过代谢组学进行分析。尽管癌细胞已经经历了代谢重编程，但耐药癌细胞的代谢进一步发生了改变。耐药细胞对化疗药物的代谢适应涉及氧化还原、脂质代谢、生物能量学、糖酵解、多胺合成等。提出的耐药代谢机制包括葡萄糖和谷氨酰胺需求增加、谷氨酰胺分解和糖酵解的活跃途径、磷酸戊糖途径中NADPH的促进、适应性线粒体重编程、脂肪酸氧化的激活以及鸟氨酸脱羧酶上调以产生多胺。有几个基因与代谢重编程和耐药性相关。干预上述调控点或靶向几个重要代谢途径中的关键基因可能会恢复细胞对化疗的敏感性。本文综述了肿瘤细胞在化疗耐药发展过程中的代谢变化，并讨论了通过代谢调控逆转化疗耐药的潜力。
