Effect of glutamine metabolism on chemoresistance and its mechanism in tumors.
Effect of glutamine metabolism on chemoresistance and its mechanism in tumors.
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DOI：
10.3724/zdxbyxb-2021-0040
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发表时间：
2021-02-25
影响因子：
--
通讯作者：
Zhu, Liyuan
中科院分区：
文献类型：
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作者：
Hu, Xinyang;Jin, Hongchuan;Zhu, Liyuan
肿瘤细胞的代谢重编程的特征在于包括谷氨酰胺在内的各种营养素的摄取增加。谷氨酰胺代谢提供糖酵解和氧化磷酸化所需的物质，并影响碳水化合物、脂肪和蛋白质代谢的稳态，从而诱导肿瘤细胞的化疗耐药性。针对谷氨酰胺代谢途径不同组分的特异性抑制剂与化疗药物联合应用对多种肿瘤均取得了良好的临床效果。谷氨酰胺代谢途径以多种方式在肿瘤细胞耐药中发挥作用。首先，谷氨酰胺转运体的动态变化可直接影响细胞内谷氨酰胺含量，从而导致耐药;其次，肿瘤基质细胞包括脂肪细胞、成纤维细胞和肿瘤微环境的代谢产物可引起免疫介导的耐药;再次，谷氨酰胺代谢关键酶的表达和活性在肿瘤耐药中也起着关键作用。本文从转运蛋白、肿瘤微环境和代谢酶等方面综述了谷氨酰胺代谢途径在肿瘤化疗耐药性形成中的作用，以期为提高耐药肿瘤的治疗效果提供参考。
The metabolic reprogramming of tumor cells is characterized by increased uptake of various nutrients including glutamine. Glutamine metabolism provides the required substances for glycolysis and oxidative phosphorylation and affects the homeostasis of carbohydrate，fat and protein metabolism to induce the chemoresistance of tumor cells. Combination of chemotherapeutic agents with inhibitors specific to different components of glutamine metabolic pathway has obtained favorable clinical results on various tumors. Glutamine metabolic pathway plays a role in drug resistance of tumor cells in various ways. Firstly，the dynamic change of glutamine transporters can directly affect intracellular glutamine content thereby causing drug resistance; secondly，tumor stromal cells including adipocyte，fibroblast and metabolite from tumor microenvironment would give rise to immune-mediated drug resistance; thirdly，the expression and activity of key enzymes in glutamine metabolism also has a critical role in drug resistance of tumors. This article reviews the effects of glutamine metabolic pathway in the development of tumor chemoresistance，in terms of transporters，tumor microenvironment and metabolic enzymes，to provide insight for improving the therapeutic efficacy for drug-resistant tumors.