氨基酸代谢重编程对肝细胞癌发生发展及治疗的影响  

The Impact of Amino Acid Metabolism Reprogramming on the Occurrence,Development,and Treatment of Hepatocellular Carcinoma

作　　者：张青 周青鸟 林文珍 ZHANG Qing;ZHOU Qing-Niao;LIN Wen-Zhen(Department of Biochemistry and Molecular Biology,School of Basic Medicine,Guangxi Medical University,Nanning 530021,Guangxi,China;Key Laboratory of Biological Molecular Medicine Research(Guangxi Medical University),Education Department of Guangxi Zhuang Autonomous Region,Nanning 530021,China)

机构地区：[1]广西医科大学基础医学院生物化学与分子生物学教研室,南宁530021 [2]广西高校生物分子医学研究重点实验室,南宁530021

出　　处：《中国生物化学与分子生物学报》2024年第10期1392-1399,共8页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.81660464,No.32260164)资助。

摘　　要：在肿瘤细胞中,特定氨基酸的改变会对癌细胞的代谢产生显著影响,并使肿瘤微环境中的免疫细胞发生改变,影响肿瘤的发生发展和治疗效果。本文首先介绍肿瘤中氨基酸的作用,从外源性氨基酸的摄入,氨基酸修饰,支链氨基酸的代谢探讨肿瘤中必需氨基酸的代谢,并阐明非必需氨基酸在非必需氨基酸营养缺陷型肿瘤中的作用。其次,阐述了氨基酸代谢重编程对肝细胞癌发生发展的影响。必需氨基酸和非必需氨基酸在肝细胞癌中存在不可或缺的作用。在肝癌细胞内,必需氨基酸含量异常升高,促进肝癌细胞的发生发展,但支链氨基酸含量的升高却存在双重作用。非必需氨基酸在肝癌细胞中常作为抑制因子发挥作用,但精氨酸可联合天冬酰胺形成正反馈循环促进肝细胞癌的发生发展。最后阐述了氨基酸代谢重编程对肝细胞癌治疗的影响。谷氨酸、丝氨酸,支链氨基酸,S-腺苷甲硫氨酸,甘氨酸,精氨酸等可作为肝细胞癌的作用靶点,抑制氧化戊二酸脱氢酶的表达可以提高肝细胞癌患者对索拉非尼的药物敏感性。肝细胞癌肿瘤微环境中的氨基酸代谢重编程促进了肝癌细胞的恶性增殖和免疫逃逸,研究其中特异性改变的氨基酸有利于为患者制定个性化的免疫治疗。In tumor cells,changes in specific amino acids can have a significant impact on the metabolism of cancer cells and alter the response of immune cells in the tumor microenvironment,affecting the occurrence,development,and therapeutic effects of tumors.This article first introduces the role of amino acids in tumors,exploring the metabolism of essential amino acids in tumors from the intake of exogenous amino acids,amino acid modification,and metabolism of branched chain amino acids,and clarify the role of nonessential amino acids in nonessential amino acid deficient tumors.Secondly,the impact of amino acid metabolism reprogramming on the occurrence and development of hepatocellular carcinoma was elucidated.Essential and nonessential amino acids play an indispensable role in hepatocellular carcinoma development.In liver cancer cells,the abnormally high content of essential amino acids promotes the occurrence and development of liver cancer cells,but the increase of branched chain amino acid content has a dual effect.Nonessential amino acids often act as inhibitory factors in liver cancer cells,but arginine can combine with asparagine to form a positive feedback loop and promote the occurrence and development of liver cancer.Finally,the impact of amino acid metabolism reprogramming on the treatment of hepatocellular carcinoma was elucidated.Glutamate,serine,branched chain amino acids,S-adenosylmethionine,glycine,arginine,etc.can serve as targets for liver cancer.Inhibiting the expression of glutarate dehydrogenase can improve the drug sensitivity of liver cancer patients to sorafenib.The reprogramming of amino acid metabolism in the tumor microenvironment of hepatocellular carcinoma promotes the malignant proliferation and immune escape of liver cancer cells.Studying the specific changes in amino acids is beneficial for developing personalized immunotherapy for patients.

关 键 词：氨基酸代谢 支链氨基酸 非必需氨基酸 肿瘤 肝细胞癌 

分 类 号：R34[医药卫生—基础医学] Q51[生物学—生物化学]