重楼皂苷抗胶质瘤作用机制的研究进展  

Research progress on the mechanism of anti-glioma action of Paris saponin

作　　者：郑淑娴 邱鹏程 王媛媛[1] 杜洋 薛玉叶 孙光强 陆云阳 汤海峰 ZHENG Shuxian;QIU Pengcheng;WANG Yuanyuan;DU Yang;XUE Yuye;SUN Guangqiang;LU Yunyang;TANG Haifeng(School of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046,China)

机构地区：[1]陕西中医药大学药学院,咸阳712046 [2]空军军医大学药学系 [3]空军特色医学中心药剂科

出　　处：《环球中医药》2022年第11期2234-2242,共9页Global Traditional Chinese Medicine

基　　金：国家自然科学基金(81973192,81903862);陕西省重点研发计划(2017SF-196,2020SF-311,2021SF-388,2021ZDLSF04-07);陕西省自然科学基金(2022JM-493);陕西省中医药管理局“秦药”开发重点科学研究项目(2021-02-ZZ-003)。

摘　　要：中药重楼具有清热解毒、消肿止痛、凉肝定惊的功效,临床常用于抗炎、抗菌、抗病毒及抗肿瘤等。重楼的主要药效成分为甾体皂苷类化合物,总称为重楼皂苷。重楼皂苷具有多种药理活性,特别是其抗肿瘤作用已引起了广泛的关注。近年来,关于其抗胶质瘤活性和作用机制的研究也越来越多。目前报道的具有抗胶质瘤活性的重楼皂苷包括重楼皂苷I(D)、II、III(薯蓣皂苷)、VI、VII和H等,它们可显著诱导胶质瘤细胞程序性死亡。其作用机制主要涉及以下几个方面:通过线粒体通路和死亡受体通路诱导胶质瘤细胞凋亡、通过释放促炎因子诱导胶质瘤细胞焦亡、通过复合物途径诱导胶质瘤细胞坏死;诱导胶质瘤细胞周期阻滞主要通过调节细胞周期蛋白和细胞周期蛋白依赖性蛋白激酶的表达水平;诱导胶质瘤细胞自噬主要通过调节与自噬有关的细胞因子如微管相关蛋白1轻链3(microtubule-associated protein 1 light chain 3,LC3)、自噬相关基因Beclin-1和泛素结合蛋白P62,从而调控AKT-mTORC1信号通路;以及通过调节上皮间质转化过程中的相关蛋白抑制胶质瘤细胞迁移侵袭。通过这些作用机制,重楼皂苷抑制胶质瘤细胞增殖从而发挥抗胶质瘤作用,同时重楼皂苷和化疗药物如替莫唑胺等联合使用可以逆转胶质瘤细胞耐药性从而增加肿瘤细胞对化疗药物的敏感性。本文对重楼皂苷抗胶质瘤的作用机制进行综述,为其作为抗胶质瘤药物的深入研发提供参考。The traditional Chinese medicine Paridis Rhizoma has the functions of clearing away heat and detoxifying, reducing swelling and pain, cooling the liver and calming convulsions. In modern clinics it was commonly used for anti-inflammatory, antibacterial, antiviral and antitumor. The main medicinal components of Paridis Rhizoma are steroidal saponins, which are often collectively referred as Paris saponin. The anti-tumor effects of Paris saponins have attracted widespread attention. In recent years, the studies on its anti-glioma effects have gradually increased. Currently reported saponins with anti-glioma activities include polyphyllins I(D), II, III(dioscin), VI, VII and H, etc. Paris saponins can induce programmed cell death in glioma cells, and mainly through mitochondrial pathway and death receptor pathway to induce glioma cells apoptosis, release pro-inflammatory factors to induce glioma cells pyroptosis, and induce glioma cells necrosis through complex pathway. Paris saponins induce glioma cell cycle is arrested by regulating the expression levels of cyclins(Cyclins) and cyclin-dependent kinases(CDKs). Paris saponins regulates the AKT-mTORC1 signaling pathway to induce glioma cells autophagy, by regulating autophagy-related cytokines such as microtubule-associated protein 1 light chain 3(LC3), autophagy related genes Beclin-1 and ubiquitin-binding protein P62. Paris saponins inhibit glioma cells migration and invasion by regulating related proteins in epithelial-mesenchymal transition(EMT) process. These mechanisms of action inhibit glioma proliferation and exert anti-glioma effects, combined with chemotherapeutic drugs such as temozolomide(TMZ) reverses drug resistance in glioma cells and increases cell sensitivity to chemotherapeutic drugs. In this article, the mechanisms of Paris saponins were reviewed to provide references for the further study of anti-glioma functions.

关 键 词：重楼皂苷 胶质瘤 作用机制 程序性死亡 细胞周期阻滞 自噬 迁移侵袭 联合用药 

分 类 号：R285[医药卫生—中药学]