Investigation and experimental validation of curcumin-related mechanisms against hepatocellular carcinoma based on network pharmacology  

作　　者：Yang CHEN Qian LI Sisi REN Ting CHEN Bingtao ZHAI Jiangxue CHENG Xiaoyan SHI Liang SONG Yu FAN Dongyan GUO 

机构地区：[1]College of Basic Medicine,Shaanxi University of Chinese Medicine,Xianyang 712046,China [2]School of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046,China [3]Medical Experimental Center,Shaanxi University of Chinese Medicine,Xianyang 712046,China [4]Shaanxi Provincial Key Laboratory of TCM Constitution and Disease Prevention,Shaanxi University of Chinese Medicine,Xianyang 712046,China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2022年第8期682-698,共17页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：supported by the General Project of Shaanxi Science and Technology Plan(No.2021JM-472);the Key Laboratory Project of Education Department of Shaanxi Province(Nos.21JS014 and 21JS007);the Subject Innovation Team of Shaanxi University of Chinese Medicine(No.2019YL14);the Postgraduate Student’s Innovation Project of Shaanxi University of Chinese Medicine(No.2021-09),China。

摘　　要：Objective:To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma(HCC)by network pharmacology and experimental in vitro validation.Methods:The predictive targets of curcumin or HCC were collected from several databases.the identified overlapping targets were crossed with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses using the Database for Annotation,Visualization,and Integrated Discovery(DAVID)platform.Two of the candidate pathways were selected to conduct an experimental verification.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium(MTT)assay was used to determine the effect of curcumin on the viability of Hep G2 and LO2 cells.The apoptosis and autophagy of Hep G2 cells were respectively detected by flow cytometry and transmission electron microscopy.Besides,western blot and real-time polymerase chain reaction(PCR)were employed to verify the p53 apoptotic pathway and adenosine 5’-monophosphate(AMP)-activated protein kinase(AMPK)autophagy pathway.Hep G2 cells were pretreated with pifithrin-α(PFT-α)and GSK690693 for further investigation.Results:The 167 pathways analyzed by KEGG included apoptosis,autophagy,p53,and AMPK pathways.The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug,regulation of apoptotic pathway,and so on.The in vitro experiments also confirmed that curcumin can inhibit the growth of Hep G2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway.Furthermore,the protein and messenger RNA(m RNA)of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group.The damage-regulated autophagy modulator(DRAM)in the PFT-α-pretreated group was downregulated,and p62 in the GSK690693-pretreated group was upregulated.Conclusions:Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1(ULK1)autophagy pathway,in which the mutual transfo

关 键 词：CURCUMIN Network pharmacology p53 Adenosine 5’-monophosphate(AMP)-activated protein kinase(AMPK) Apoptosis AUTOPHAGY 

分 类 号：R285.6[医药卫生—中药学]