摘要
Correa级联反应是描述慢性胃炎逐步进展为胃癌的经典模型,将胃癌的发展大致分为胃炎、胃癌前病变和胃癌3个阶段。葡萄糖代谢重编码作为胃癌的显著特征,贯穿于Correa级联反应的全过程。在慢性胃炎阶段,幽门螺杆菌感染等诱发的炎症微环境可激活糖酵解,抑制胃黏膜损伤的修复。在胃癌前病变阶段,代谢重编码进一步增强,通过抑制凋亡、促进增殖发挥核心作用。在胃癌阶段,代谢重编码则成为肿瘤增殖、侵袭与耐药的核心动力。中医药在防治胃癌方面具有多靶点整合调控的独到优势。文章基于葡萄糖代谢重编码调控Correa级联反应的分子机制,系统总结了中医药调控Correa级联反应中葡萄糖代谢重编程的最新研究进展:中药能显著调节己糖激酶2、丙酮酸激酶M2型和乳酸脱氢酶A等糖代谢关键酶的活性与表达,直接抑制糖酵解通量,减少乳酸生成,促进损伤胃黏膜细胞修复;黄芪甲苷、小檗碱等中药活性成分及复方可通过抑制改为磷脂酰肌醇-3激酶(Phosphatidylinositol-3 Kinase PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mammalian Target of Rapamycin,mTOR)、缺氧诱导因子-1α(Hypoxia Inducible Foctor-1α,HIF-1α)和Wnt/β-catenin等关键信号通路,从上游逆转促糖酵解信号的传导,诱导肿瘤细胞凋亡;或直接调控c-Myc、肿瘤蛋白p53等相关基因与蛋白的表达,抑制胃癌细胞恶性增殖和侵袭;此外,中药还通过改善肿瘤免疫微环境、诱导氧化应激等间接调控代谢重编程,以期为中医药防治的胃癌寻找新的靶点,为后续研究提供参考。
The Correa cascade reaction represents a classic model describing the progressive development of chronic gastritis into gastric cancer,broadly categorizing gastric cancer progression into three stages:gastritis,precancerous gastric lesions,and gastric cancer.Glucose metabolic reprogramming,a hallmark feature of gastric cancer,persists throughout the entire Correa cascade reaction.During the chronic gastritis stage,the inflammatory microenvironment induced by factors such as Helicobacter pylori infection activates glycolysis and inhibits the repair of damaged gastric mucosa.In the precancerous gastric lesions stage,glucose metabolism recoding intensifies,playing a central role by suppressing apoptosis and promoting proliferation.At the stage of gastric cancer,it becomes the core driver of tumor proliferation,invasion,and drug resistance.Traditional Chinese medicine(TCM)possesses unique advantages in gastric cancer prevention and treatment through its multi-target integrated regulation.Based on the molecular mechanism of glucose metabolism recoding regulating the Correa cascade reaction,this paper systematically summarizes the latest research advances in TCM’s multi-target,multi-stage regulation of glucose metabolic recoding within the Correa cascade reaction:TCM significantly modulates the activity and expression of key glucose metabolism enzymes such as hexokinase 2,pyruvate kinase M2,and lactate dehydrogenase A,directly inhibiting glycolytic flux,reducing lactate production,and promoting repair of damaged gastric mucosal cells.Active components and formulas such as astragaloside IV and berberine can inhibit key signaling pathways including PI3K/Akt/mTOR,HIF-1α,and Wnt/β-catenin pathways to reverse pro-glycolytic signaling upstream,inducing tumor cell apoptosis.Alternatively,they directly regulate the expression of genes and proteins such as c-Myc and P53,inhibiting malignant proliferation and invasion of gastric cancer cells.Furthermore,TCM indirectly modulates metabolic reprogramming by improving the tumor immune microenvironment and inducing oxidative stress.This aims to identify novel targets for gastric cancer prevention and treatment using TCM,providing reference for subsequent research.
出处
《中医临床研究》
2025年第30期10-20,共11页
Clinical Journal Of Chinese Medicine
基金
基于中医浊毒理论探讨健脾化浊解毒法调控“上皮-基质”代谢耦联逆转胃癌前状态的机制研究(23PY02)。
关键词
中医药
Correa级联反应
葡萄糖代谢重编码
中医治疗
Traditional Chinese medicine
Correa cascade reaction
Glucose metabolism recoding
Traditional Chinese medicine treatment
