基于网络药理学和实验验证探讨芝麻林素抗肝细胞癌作用及其机制

TS201.4; 为了探究芝麻林素对肝细胞癌的抗肿瘤作用及其分子机制,通过网络药理学分析,预测芝麻林素与肝细胞癌的交集靶点,以及交集靶点富集的通路和生物学过程,然后检索SwissADME数据库分析芝麻林素的药代动力学.采用CCK8法检测细胞活性,采用Annexin V-FITC/PI双染法、流式细胞术、蛋白免疫印迹法、细胞迁移法分析芝麻林素处理后Huh-7细胞凋亡、周期阻滞及迁移抑制的作用与机制.结果表明,网络药理学分析可得交集靶点共64个,基因本体论功能共352个,京都基因与基因组百科全书信号通路共136个.体外细胞实验表明芝麻林素可以通过调控活性氧(reactive oxygen spec...

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Published in食品科学 Vol. 45; no. 15; pp. 22 - 39
Main Authors 曹荣安, 张佳苗, 侯文爽, 王安琪, 关俊东, 金成浩
Format Magazine Article
LanguageChinese
Published 黑龙江八一农垦大学食品学院,黑龙江大庆 163319%黑龙江八一农垦大学生命科学技术学院,黑龙江大庆 163319 15.08.2024
黑龙江八一农垦大学国家杂粮工程技术中心,黑龙江大庆 163319
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ISSN1002-6630
DOI10.7506/spkx1002-6630-20231213-100

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Abstract TS201.4; 为了探究芝麻林素对肝细胞癌的抗肿瘤作用及其分子机制,通过网络药理学分析,预测芝麻林素与肝细胞癌的交集靶点,以及交集靶点富集的通路和生物学过程,然后检索SwissADME数据库分析芝麻林素的药代动力学.采用CCK8法检测细胞活性,采用Annexin V-FITC/PI双染法、流式细胞术、蛋白免疫印迹法、细胞迁移法分析芝麻林素处理后Huh-7细胞凋亡、周期阻滞及迁移抑制的作用与机制.结果表明,网络药理学分析可得交集靶点共64个,基因本体论功能共352个,京都基因与基因组百科全书信号通路共136个.体外细胞实验表明芝麻林素可以通过调控活性氧(reactive oxygen species,ROS)介导的丝裂原活化蛋白激酶/信号转导与转录激活因子3/核因子κB和磷脂酰肌醇3激酶(phosphatidylinositol 3-kinases,PI3K)/蛋白激酶B(protein kinase B,AKT)信号通路,诱导Huh-7细胞线粒体依赖性凋亡与G2/M期阻滞.同时,芝麻林素通过ROS介导的PI3K/AKT/糖原合成酶激酶-3β(glycogen synthase kinase-3β,GSK-3β)/β-连环蛋白信号通路抑制细胞迁移.最后,SwissADME分析结果表明芝麻林素具有良好的类药性.综上,芝麻林素可以通过ROS介导的信号通路诱导Huh-7细胞发生细胞凋亡、周期阻滞与抑制迁移作用.
AbstractList TS201.4; 为了探究芝麻林素对肝细胞癌的抗肿瘤作用及其分子机制,通过网络药理学分析,预测芝麻林素与肝细胞癌的交集靶点,以及交集靶点富集的通路和生物学过程,然后检索SwissADME数据库分析芝麻林素的药代动力学.采用CCK8法检测细胞活性,采用Annexin V-FITC/PI双染法、流式细胞术、蛋白免疫印迹法、细胞迁移法分析芝麻林素处理后Huh-7细胞凋亡、周期阻滞及迁移抑制的作用与机制.结果表明,网络药理学分析可得交集靶点共64个,基因本体论功能共352个,京都基因与基因组百科全书信号通路共136个.体外细胞实验表明芝麻林素可以通过调控活性氧(reactive oxygen species,ROS)介导的丝裂原活化蛋白激酶/信号转导与转录激活因子3/核因子κB和磷脂酰肌醇3激酶(phosphatidylinositol 3-kinases,PI3K)/蛋白激酶B(protein kinase B,AKT)信号通路,诱导Huh-7细胞线粒体依赖性凋亡与G2/M期阻滞.同时,芝麻林素通过ROS介导的PI3K/AKT/糖原合成酶激酶-3β(glycogen synthase kinase-3β,GSK-3β)/β-连环蛋白信号通路抑制细胞迁移.最后,SwissADME分析结果表明芝麻林素具有良好的类药性.综上,芝麻林素可以通过ROS介导的信号通路诱导Huh-7细胞发生细胞凋亡、周期阻滞与抑制迁移作用.
Abstract_FL This study aimed to investigate the anti-tumor effect of sesamolin(SES)on hepatocellular carcinoma(HCC)and its molecular mechanism using network pharmacology and experimental verification.The intersecting targets between SES and HCC and their signaling pathways and biological processes were predicted by network pharmacological analysis.The pharmacokinetics properties of SES were analyzed through search against the SwissADME database.The cell count kit-8(CCK-8)method was used to detect the cell viability.Annexin V-FITC/PI double staining,flow cytometry,Western blotting and cell migration assays were used to analyze the effect and mechanism of SES on cell apoptosis,cell cycle arrest and migration inhibition in Huh-7 cells.The results showed that a total of 64 intersecting targets,352 Gene Ontology(GO)functions and 136 Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways were identified by network pharmacological analysis.The in vitro test showed that SES induced mitochondria-dependent apoptosis and G2/M phase arrest in Huh-7 cells through regulating the mitogen-activated protein kinase(MAPK)/signal transducer and activator of transcription-3(STAT3)/nuclear factor κB(NF-κB)and phosphatidylinositol 3-kinases(PI3K)/protein kinase B(AKT)signaling pathways mediated by reactive oxygen species(ROS).Meanwhile,SES inhibited cell migration through the ROS-mediated PI3K/AKT/glycogen synthase kinase-3β(GSK-3β)/β-catenin signaling pathway.Finally,SwissADME analysis showed that the SES exhibited excellent druglike properties.In conclusion,sesamolin could induce apoptosis,cell cycle arrest and inhibit migration in Huh-7 cells through the ROS-mediated signaling pathways.
Author 王安琪
侯文爽
张佳苗
金成浩
曹荣安
关俊东
AuthorAffiliation 黑龙江八一农垦大学食品学院,黑龙江大庆 163319%黑龙江八一农垦大学生命科学技术学院,黑龙江大庆 163319;黑龙江八一农垦大学国家杂粮工程技术中心,黑龙江大庆 163319
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Author_FL GUAN Jundong
JIN Chenghao
HOU Wenshuang
WANG Anqi
CAO Rong'an
ZHANG Jiamiao
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DocumentTitle_FL Network Pharmacological Analysis and Experimental Verification of the Anti-hepatocellular Carcinoma Activity and Mechanism of Sesamolin
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Issue 15
Keywords 网络药理学
细胞凋亡
细胞周期
细胞迁移
sesamolin
肝细胞癌
network pharmacology
cell cycle
芝麻林素
cell apoptosis
cell migration
hepatocellular carcinoma
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PublicationTitle 食品科学
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Publisher 黑龙江八一农垦大学食品学院,黑龙江大庆 163319%黑龙江八一农垦大学生命科学技术学院,黑龙江大庆 163319
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Snippet TS201.4; 为了探究芝麻林素对肝细胞癌的抗肿瘤作用及其分子机制,通过网络药理学分析,预测芝麻林素与肝细胞癌的交集靶点,以及交集靶点富集的通路和生物学过程,然后检...
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StartPage 22
Title 基于网络药理学和实验验证探讨芝麻林素抗肝细胞癌作用及其机制
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