槐定碱衍生物抑制肝癌细胞迁移与侵袭研究  

Sophoridine Derivative Against Liver Cancer Cell Migration and Invasion

作　　者：吴黎川 谈振凯 覃业浩 赵续棋 谢雨心 黄丽羽 韦金锐 WU Lichuan;TAN Zhenkai;QIN Yehao;ZHAO Xuqi;XIE Yuxin;HUANG Liyu;WEI Jinrui(School of Medicine,Guangxi University,Nanning Guangxi 530004,China;Guangxi Key Laboratory of Special Biomedicine(Guangxi University),Nanning Guangxi 530004,China;Institute of Traditional Chinese and Zhuang-Yao Ethnic Medicine,Guangxi University of Chinese Medicine,Nanning Guangxi 530200,China)

机构地区：[1]广西大学医学院,广西南宁530004 [2]广西特色生物医药重点实验室(广西大学),广西南宁530004 [3]广西中医药大学中医药壮瑶医药研究院,广西南宁530200

出　　处：《广西师范大学学报(自然科学版)》2025年第2期207-220,共14页Journal of Guangxi Normal University:Natural Science Edition

基　　金：国家自然科学基金(82260715);广西中青年教师基础能力提升项目(2024KY0302);广西研究生教育创新计划资助项目(YCSW2024026)。

摘　　要：本文综合运用网络药理学、生物信息学、分子对接、分子动力学、转录组学及体外实验探究一种含酯基吲哚类槐定碱衍生物对肝癌细胞迁移与侵袭的作用及机制。通过PharmMapper、Super-PRED、Swisstarget及Targetnet数据库查找衍生物潜在靶点,利用差异表达分析确定肝癌转移相关基因,取交集确定衍生物作用的肝癌转移相关基因,通过GO/KEGG分析,预测衍生物潜在作用信号通路和差异基因富集信号通路,利用蛋白互作分析和分子对接及分子动力学模拟确定核心靶点和衍生物与核心靶点的相互作用,利用转录组测序获取衍生物导致的差异表达基因,通过蛋白免疫印迹实验检测相应蛋白的表达。结果表明:衍生物可显著抑制肝癌细胞的迁移和侵袭,共有衍生物潜在作用肝癌转移相关靶点47个,其中核心靶点5个:STAT3、PPARG、MAP2K1、CDK4、AKT3;MAPK通路在衍生物预测基因及衍生物导致的差异表达基因富集分析中显著富集,衍生物与核心靶点MAP2K1(MAPK通路关键节点)具备较高结合亲和度,MAPK通路中的核心成员p-Erk1/2蛋白表达下调。这些都表明含酯基吲哚类槐定碱衍生物通过降低MAPK/ERK通路活性抑制肝癌细胞迁移与侵袭。This study comprehensively applies network pharmacology,bioinformatics,molecular docking,molecular dynamics,transcriptomics,and in vitro experiments to explore the effects and mechanisms of an indole sophoridine derivative containing ester group on the migration and invasion of liver cancer cells.The potential targets of this derivative were retrieved by using PharmMapper,Super-PRED,Swisstarget,and Targetnet databases.Liver cancer metastasis related genes were determined through differential expression analysis.The anti-liver cancer metastasis targets of this derivative were identified by taking intersection between predicted targets of this derivative and liver cancer metastasis related genes.GO/KEGG enrichment analysis was conducted to predict the potential signaling pathways of this derivative.Core targets of this derivative were identified via using protein-protein interaction analysis.Subsequently,molecular docking and molecular dynamics were involved to reveal the potential interaction between this derivative could core target.Furthermore,transcriptome sequencing was performed to obtain differentially expressed genes caused by this derivative.Finally,western blot assays were conducted to validate the effects of this derivative on MAPK pathway.The results showed that this derivative could significantly inhibit the migration and invasion of liver cancer cells.A total of 47 potential liver cancer metastasis related targets were predicted for this derivative,including 5 core targets:STAT3,PPARG,MAP2K1,CDK4,AKT3.The MAPK pathway was significantly enriched in the analysis of predicted genes and differentially expressed genes caused by this derivative.Molecular docking and molecular dynamics simulations also showed that this derivative had a high binding affinity with the core target MAP2K1(a key node of the MAPK pathway).The results of western blot showed that under this derivative treatment,the core member of the MAPK pathway,p-Erk1/2 protein expression,was downregulated.Conclusion:this indole sophorodine deriva

关 键 词：肝癌 细胞迁移与侵袭 槐定碱衍生物6j 网络药理学 分子对接 分子动力学模拟 MAPK通路 

分 类 号：R285[医药卫生—中药学]