基于PI3K/Akt/mTOR信号通路中医药治疗胃癌作用机制的研究进展  

Research progress on mechanism of traditional Chinese medicine in treating gastric cancer based on PI3K/Akt/mTOR signaling pathway

作　　者：贾福运 高晟玮 马佳乐 秦云普 苏禹如 朱婷婷[1] 高望[2] JIA Fuyun;GAO Shengwei;MA Jiale;QIN Yunpu;SU Yuru;ZHU Tingting;GAO Wang(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津中医药大学,301617 [2]天津中医药大学第二附属医院消化科

出　　处：《环球中医药》2022年第1期165-172,共8页Global Traditional Chinese Medicine

基　　金：国家中医药管理局第六批全国老中医药专家学术经验继承工作室(国中医药人教发[2017]29号)。

摘　　要：磷脂酰肌醇-3-激酶(phosphatidylinositol 3-kinases,PI3K)及其下游的蛋白激酶B(protein kinase B,PKB/Akt)、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)组成的PI3K/Akt/mTOR信号通路在调控肿瘤细胞的生长、凋亡和迁移中发挥重要的作用。中医药领域以PI3K/Akt/mTOR信号通路为切入点,进行了中药单体及有效成分、中药复方干预胃癌中PI3K/Akt/mTOR信号通路的临床研究取得了一定突破,并将中医药的作用机制归纳为4类:(1)调节抗凋亡Bcl-2蛋白及促凋亡Bax蛋白之间的平衡、上调Caspase-3、9相关基因蛋白及线粒体通路诱导细胞凋亡;(2)增加自噬溶酶体数量及自噬体囊泡,促使自噬相关基因Atg复合体的产生,提升LC3-Ⅱ/LC3-Ⅰ自噬比值水平及相关蛋白Beclin-1、p62诱导胃癌细胞自噬;(3)促进缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)高表达和缺氧诱导因子的释放进而激活血管内皮生长因子(vascular endothelial growth factor,VEGF)促进血管形成;(4)调节特定miRNA中miR-21及miR-10a表达抑制肿瘤细胞生长。Gastric cancer is a malignant tumor with an increasing incidence rate.Because of the early stage of illness,the symptoms are not typical.Most of the patients have reached the advanced stage when they are diagnosed,which seriously threatens the life and health.With the development of gastric cancer research in recent years,the molecular signaling pathways that induce gastric cancer have been well known.The PI3K/Akt/mTOR signaling pathway composed of phosphatidylinositol-3-kinase(PI3K)and its downstream protein kinase B(Akt)and rapamycin target protein(mTOR)is closely related to gastric cancer.It plays an important role in apoptosis and migration.Traditional Chinese medicine(TCM)adopts such characteristic concepts as"holistic concept"and"syndrome differentiation and treatment"to give full play to its unique advantages in the treatment of gastric cancer.Molecular biology research shows that the advantages of traditional Chinese medicine in anti-tumor such as multi-target,multi-channel,less side effects have attracted much attention,and it has significant effect in the treatment of gastric cancer.PI3K/Akt/mTOR signaling pathway was taken as the breakthrough point in the field of traditional Chinese medicine.The clinical research on the intervention of traditional Chinese medicine monomers,active ingredients and Chinese medicine compound on PI3K/Akt/mTOR signaling pathway in gastric cancer was carried out.The mechanism of action of traditional Chinese Medicine was summarized into four categories:(1)Regulating the balance between anti apoptotic Bcl-2 protein and pro apoptotic Bax protein,up-regulation of Caspase-3,up-regulation of apoptosis of Bcl-2 protein,apoptosis induced by up-regulation of Caspase-3 and Caspase-9 related gene and protein,mitochondrial pathway.(2)Autophagy induced by increasing the number of autophagy lysosomes and autophagy vesicles,promoting the production of autophagy related gene ATG complex,increasing the autophagy ratio of LC3-Ⅱ/LC3-Ⅰand related proteins beclin-1 and p62(3)Promoting HIF-1

关 键 词：中医药 磷脂酰肌醇-3-激酶 蛋白激酶B 雷帕霉素靶蛋白 胃癌 PI3K/Akt/mTOR信号通路 

分 类 号：R273[医药卫生—中西医结合]