《生命科学》 2025, 37(10): 1360-1371

GLUL在肝细胞癌耐药机制中的研究进展

韩卓卓^1,2 , 汪　浩³ , 赵　健^1,2,*

¹上海中医药大学，上海 201203 ²上海健康医学院，上海市分子影像学重点 实验室，上海 201318 ³北部战区空军医院肿瘤科，沈阳 110042

摘　要：

肝细胞癌(HCC) 是全球最常见的原发性肝癌类型，耐药问题严重影响治疗效果与患者预后。谷氨酰胺合成酶(GLUL) 作为谷氨酰胺代谢的限速酶，在HCC 中高表达，参与调控肿瘤细胞的代谢重编程、信号通路激活和免疫逃逸等多种过程，是耐药机制中的关键节点。GLUL 通过mTOR、Wnt/β-catenin 等信号通路增强HCC 细胞的治疗适应性与生存能力。本文系统综述了GLUL 在HCC 中的表达特征、生物学功能及其与耐药机制的关联，提出其作为治疗靶点的潜力，并探讨了冬凌草、苦参、鸦胆子等天然产物在联合干预GLUL 通路中的应用前景，旨在为HCC 耐药的精准治疗提供新靶点与策略依据。

通讯作者：赵　健 , Email:zhaoj_24@sumhs.edu.cn

Research progress on GLUL in drug resistance mechanisms of hepatocellular carcinoma

HAN Zhuo-Zhuo^1,2 , WANG Hao³ , ZHAO Jian^1,2,*

¹Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China ²Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China ³Department of Oncology, The Air Force Hospital of Northern Theater PLA, Shenyang 110042, China

Abstract:

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancers worldwide, and drug resistance significantly affects treatment outcomes and patient prognosis. Glutamine synthetase (GLUL), a ratelimiting enzyme in glutamine metabolism, is highly expressed in HCC and plays a crucial role in regulating metabolic reprogramming, signaling pathway activation, and immune evasion in tumor cells. GLUL enhances the therapeutic adaptability and survival of HCC cells through signaling pathways such as mTOR and Wnt/β-catenin, making it a key player in drug resistance mechanisms. This article provides a comprehensive review of the expression patterns, and biological functions of GLUL, and its role in drug resistance in HCC, highlighting its potential as a therapeutic target. Additionally, the article explores the prospects of natural compounds such as Rabdosia rubescens (Donglingcao), Sophora flavescens(Kushen), and Brucea javanica (Yadanzi) in combination therapies targeting GLUL pathways, aiming to offer new targets and strategic insights for precision treatment of drug-resistant HCC.

Communication Author：ZHAO Jian , Email:zhaoj_24@sumhs.edu.cn