Curcumin for gastric cancer:Mechanism prediction via network pharmacology,docking,and in vitro experiments  

作　　者：Peng-Hui Yang Ya-Nan Wei Bi-Juan Xiao Si-Yi Li Xin-Long Li Liang-Jun Yang Hua-Feng Pan Geng-Xin Chen 

机构地区：[1]The Second School of Clinical Medicine,Guangzhou University of Chinese Medicine,Guangzhou 510006,Guangdong Province,China [2]Science and Technology Innovation Center,Guangzhou University of Chinese Medicine,Guangzhou 510006,Guangdong Province,China [3]Department of Traditional Chinese Medicine,The People's Hospital of Longhua,Shenzhen 518109,Guangdong Province,China [4]Department of Gastroenterology,Tongde Hospital of Zhejiang Province,Hangzhou 310012,Zhejiang Province,China [5]Centre for Translational Medicine,The Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510120,Guangdong Province,China

出　　处：《World Journal of Gastrointestinal Oncology》2024年第8期3635-3650,共16页世界胃肠肿瘤学杂志（英文版）（电子版）

基　　金：Supported by the National Nature Science Foundation of China,No.81273735 and No.82174319;the Natural Science Foundation of Guangdong Province,China,No.2021A1515010961;the Key-Area Research and Development Program of Guangdong Province,China,No.2020B1111100011;the China Postdoctoral Science Foundation,China,No.2023M740859.

摘　　要：BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.AIM To elucidate the potential mechanisms of curcumin in the treatment of GC.METHODS Network pharmacological approaches were used to perform network analysis of Curcumin.We first analyzed Lipinski’s Rule of Five for the use of Curcumin.Curcumin latent targets were predicted using the PharmMapper,SwissTargetPrediction and DrugBank network databases.GC disease targets were mined through the GeneCard,OMIM,DrugBank and TTD network databases.Then,GO enrichment,KEGG enrichment,protein-protein interaction(PPI),and overall survival analyses were performed.The results were further verified through molecular docking,differential expression analysis and cell experiments.RESULTS We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets.The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways.Following PPI analysis,6 hub targets were identified,namely,estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),cytochrome P450 family 3 subfamily A member 4(CYP3A4),mitogen-activated protein kinase 14(MAPK-14),cytochrome P450 family 1 subfamily A member 2(CYP1A2),and cytochrome p450 family 2 subfamily B member 6(CYP2B6).These factors are correlated with decreased survival rates among patients diagnosed with GC.Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes.The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation.mRNA levels of hub targets CYP3A4,MAPK14,CYP1A2,and CYP2B6 in BGC-823 cells were significantly increased in each dose group.CONCLUSION Curcumin can play an anti-GC role through a variety of targets,pathways and biological processes.

关 键 词：CURCUMIN Gastric cancer Network pharmacology Molecular docking Survival analysis 

分 类 号：R735.2[医药卫生—肿瘤]