摘要
目的探讨芍药内酯苷体外抗肝癌的作用及其机制。方法采用CCK8法检测不同浓度芍药内酯苷对HepG2细胞活性的影响。采用transwell法检测芍药内酯苷对HepG2迁移侵袭能力的影响。通过转录组学分析芍药内酯苷在体外作用于HepG2细胞的分子机制。结果HepG2细胞随着芍药内酯苷浓度升高,存活率显著下降,芍药内酯苷终浓度为200μmol·L^(-1)时,HepG2细胞存活率为54%,能显著抑制肝癌细胞侵袭(P<0.05)。与对照组相比,实验组细胞转录组学测序中得到340个差异表达基因,其中上调基因154个,下调基因186个,GO功能中,富集到BP的差异基因,主要涉及到半乳糖基神经酰胺生物合成、IL13的细胞应答和钙离子跨膜转运等过程;富集到CC的差异基因,主要涉及到核内膜和核膜部分的组成;富集到MF的差异基因,主要涉及到胆碱跨膜转运蛋白活性。在KEGG功能分析中,共筛选得到8条具有统计学差异的生物通路,主要集中在信号转导、代谢活动、神经活性等方面。结论芍药内酯苷在体外实验中对HepG2细胞具有抑制增殖与降低侵袭作用,可能是通过调节信号转导、代谢活动、神经活性、钙离子跨膜转运等通路上的BDKRB1、TUBA8、ADRB1、GRM1等基因实现的。
Objective To determine the anti-hepatoma effect of albiflorin in vitro and its mechanism.Methods CCK8 assay was used to detect the effect of albiflorin at different concentrations on the activity of HepG2 cells.The effect of albiflorin on the migration and invasion of HepG2 cells was detected by transwell method.The molecular mechanism of albiflorin on HepG2 cells in vitro was analyzed by transcriptomics.Results The survival rate of HepG2 cells decreased significantly with the increase of albiflorin concentration,and the survival rate was 54%at 200μmol·L-1.When the concentration of albiflorin was 200μmol·L^(-1),the invasion of hepatocellular carcinoma cells was significantly inhibited(P<0.05).Compared with the control group,340 differentially expressed genes were found in the experimental group,including 154 up-regulated genes and 186 down-regulated genes.The differential genes enriched in the GO function were mainly involved in galactosylceramide biosynthesis,IL13 cell response and calcium transmembrane transport in BP;the enrichment of CC was mainly related to the composition of nuclear intima and nuclear membrane.In MF they were mainly related to the activity of choline transmembrane transporter.In the functional analysis of KEGG,8 biological pathways with statistical differences were screened,mainly focusing on signal transduction,metabolic activity,neural activity and so on.Conclusion Albiflorin can inhibit the proliferation and invasion of HepG2 cells in vitro,whose mechanism may be to regulate BDKRB1,TUBA8,ADRB1,GRM1 and other genes on the signal transduction,metabolic activity,neural activity and calcium ion transmembrane transport pathways.
作者
周雅婷
罗志强
张彬彬
王武斌
孙睿
于国华
史渊源
ZHOU Ya-ting;LUO Zhi-qiang;ZHANG Bin-bin;WANG Wu-bin;SUN Rui;YU Guo-hua;SHI Yuan-yuan(School of Life Sciences,Beijing University of Chinese Medicine,Beijing 102488;Shenzhen Research Institute,Beijing University of Chinese Medicine,Shenzhen 518118)
出处
《中南药学》
CAS
2021年第6期1074-1079,共6页
Central South Pharmacy
基金
中医智能化健康干预及管理技术平台的建立(编号:2019YFC1710105)。
关键词
肝癌
芍药内酯苷
转录组测序
作用机制
liver cancer
albiflorin
transcriptomics sequencing
mechanism