Targeting colorectal cancer with Herba Patriniae and Coix seed:Network pharmacology,molecular docking,and in vitro validation  

作　　者：Cheng-Lei Wang Bing-Wei Yang Xin-Yan Wang Xue Chen Wei-Dong Li Hao-Yu Zhai Ying Wu Mu-YaoCui Jia-He Wu Qing-Hui Meng Nan Zhang 

机构地区：[1]Department of Oncology,Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China [2]The First Clinical Medical College,Shaanxi University of Chinese Medicine,Xianyang 712046,Shaanxi Province,China [3]Department of Scientific Research Management,Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China [4]School of Clinical Medicine Qinghai University,Xining 810000,Qinghai Province,China [5]School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China

出　　处：《World Journal of Gastrointestinal Oncology》2024年第8期3539-3558,共20页世界胃肠肿瘤学杂志（英文版）（电子版）

基　　金：Supported by the National Natural Science Foundation of China,No.82174464;China Academy of Traditional Chinese Medicine Science and Technology Innovation Project,No.CI2021A01806;Central High Level Traditional Chinese Medicine Hospital Clinical Research and Achievement Transformation Ability Enhancement Project,No.HLCMHPP2023085.

摘　　要：BACKGROUND Herba Patriniae and Coix seed(HC)constitute a widely utilized drug combination in the clinical management of colorectal cancer(CRC)that is known for its diuretic,anti-inflammatory,and swelling-reducing properties.Although its efficacy has been demonstrated in a clinical setting,the active compounds and their mechanisms of action in CRC treatment remain to be fully elucidated.AIM To identify the active,CRC-targeting components of HC and to elucidate the mechanisms of action involved.METHODS Active HC components were identified and screened using databases.Targets for each component were predicted.CRC-related targets were obtained from human gene databases.Interaction targets between HC and CRC were identified.A“drug-ingredient-target”network was created to identify the core components and targets involved.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were conducted to elucidate the key pathways involved.Molecular docking between core targets and key components was executed.In vitro experiments validated core monomers.RESULTS Nineteen active components of HC were identified,with acacetin as the primary active compound.The predictive analysis identified 454 targets of the active compounds in HC.Intersection mapping with 2685 CRC-related targets yielded 171 intervention targets,including 30 core targets.GO and KEGG analyses indicated that HC may influence the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway.Molecular docking showed that acacetin exhibited an optimal interaction with AKT1,identifying PI3K,AKT,and P53 as key genes likely targeted by HC during CRC treatment.Acacetin inhibited HT-29 cell proliferation and migration,as well as promoted apoptosis,in vitro.Western blotting analysis revealed increased p53 and cleaved caspase-3 expression and decreased levels of p-PI3K,p-Akt,and survivin,which likely contributed to CRC apoptosis.CONCLUSION Acacetin,the principal active compound in the HC pair,inhibited the proliferation and migration of HT-29 cells and promoted

关 键 词：Colorectal cancer Baijiangcao(Herba Patriniae) Yiyiren(Coix seed) ACACETIN PROLIFERATION MIGRATION Apoptosis Network pharmacology 

分 类 号：R735.34[医药卫生—肿瘤]