牛蒡子苷元衍生物对肿瘤细胞的抑制作用及其机制研究  

Inhibitory Effect of Arctigenin Derivatives on Tumor Cells and Its Mechanism

作　　者：刘芳菲 舒晖 刘丁瑞 张欣宏 朱颜铂 赵岩[1] 蔡恩博[1] 韩佳宏[1] LIU Fangfei;SHU Hui;LIU Dingrui;ZHANG Xinhong;ZHU Yanbo;ZHAO Yan;CAI Enbo;HAN Jiahong(College of Chinese Medicinal Material,Jilin Agricultural University,Changchun 130118,China;Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education,Stem Cell and Cancer Center,the First Hospital of Jilin University,Changchun 130021,China)

机构地区：[1]吉林农业大学中药材学院,长春130118 [2]吉林大学第一医院干细胞与肿瘤中心器官再生与移植教育部重点实验室,长春130021

出　　处：《中国细胞生物学学报》2024年第6期1171-1180,共10页Chinese Journal of Cell Biology

基　　金：吉林省科技发展计划(批准号:20210101234JC)资助的课题

摘　　要：在该研究中,共设计出27种牛蒡子苷元衍生物,其中9种为新型靶向肿瘤细胞线粒体的衍生物。生物学研究表明,与牛蒡子苷元相比,所有连接有三苯基膦的化合物的抗肿瘤活性均有大幅度的提高。其中,Mito-ARG-7对A549细胞显示出高度的选择性,其抗肿瘤活性相对于牛蒡子苷元增加了86.38%。其研究表明,Mito-ARG-7的抗肿瘤机制包括明显增加A549细胞内活性氧的产生量,引起细胞线粒体膜电位下降,促进内源性线粒体凋亡信号通路上的凋亡蛋白Cytochrome C自线粒体向细胞质的释放,以及引起Caspase家族蛋白的活化,最终诱发肿瘤细胞的凋亡。该研究合成的具有线粒体靶向功能的新型牛蒡子苷元衍生物为靶向抗肿瘤药物的研发提供了参考。In this study,a total of 27 ARG(arctigenin)derivatives were designed,of which nine were novel derivatives targeting tumor cell mitochondria.Biological studies showed that all the triphenylphosphine conjugated compounds had a significant increase in anti-tumor activity compared with ARG.Among them,Mito-ARG-7 showed a high selectivity against A549 cells,and its anti-tumor activity was increased by 86.38%compared with ARG.This study showed that the anti-tumor mechanisms of Mito-ARG-7 included significantly increasing the production of reactive oxygen species in A549 cells,causing a decrease in mitochondrial membrane potential,promoting the release of apoptotic protein Cytochrome C from mitochondria to cytoplasm in the endogenous mitochondrial apoptosis signaling pathway,and causing the activation of Caspase family proteins to eventually induce the apoptosis of tumor cells.The novel arctigenin derivative with mitochondrial targeting function synthesized in this study provides a reference for the development of targeted anti-tumor drugs.

关 键 词：牛蒡子苷元衍生物 A549细胞 线粒体途径 细胞凋亡 

分 类 号：R285[医药卫生—中药学]