Epigallocatechin gallate inhibits dimethylhydrazine-induced colorectal cancer in rats  

作　　者：Yu Wang Hei-Ying Jin Ming-Zhi Fang Xiao-Feng Wang Hao Chen Shu-Liang Huang De-Song Kong Min Li Xiu Zhang Yu Sun Shui-Ming Wang 

机构地区：[1]Department of Oncology,Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,Nanjing 210001,Jiangsu Province,China [2]Department of Colorectal Surgery,The Second Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210000,Jiangsu Province,China [3]National Center of Colorectal Disease,Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,Nanjing 210001,Jiangsu Province,China [4]Department of Pathology,Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,Nanjing 210022,Jiangsu Province,China [5]Scientific Research Administration Department,Nanjing Hospital of Chinese Medicine affiliated to Nanjing University of Chinese Medicine,Nanjing 210001,Jiangsu Province,China [6]Endoscopy Center,Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,Nanjing 210001,Jiangsu Province,China [7]Origin Bioscience Inc,Nanjing 210000,Jiangsu Province,China

出　　处：《World Journal of Gastroenterology》2020年第17期2064-2081,共18页世界胃肠病学杂志（英文版）

基　　金：Supported by Nursing Advantage Discipline Construction Project Foundation of Jiangsu Province University,No.2019YSHL107;Nanjing Medical Science and Technique Development Foundation,No.NWQR-201705.

摘　　要：BACKGROUND Epigallocatechin gallate(EGCG)is a polyhydroxy phenolic compound extracted from tea and its antitumor effect has received widespread attention.We explored the inhibitory effect of EGCG on dimethylhydrazine(DMH)-induced colorectal cancer(CRC)using a rat model,predicted the interaction between EGCG and CRC target genes using a database,and explained the EGCG associated target pathways and mechanisms in CRC.AIM To understand the inhibitory mechanisms of EGCG on CRC cell proliferation and identify its pharmacological targets by network pharmacology analysis.METHODS DMH(40 mg/kg,s.c.,twice weekly for eight weeks)was used to induce CRC in rats.After model establishment,the rats were administered with EGCG(50,100,or 200 mg/kg,p.o.,once daily for eight weeks)and killed 12 and 20 wk after the start of the experiment.Formation of aberrant crypt foci and tumor was studied by histological analysis.Using network pharmacology analysis,candidate and collective targets of EGCG and CRC were identified,and Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes analyses were used to predict the pathways altered by EGCG.RESULTS At week 12,high-dose EGCG treatment significantly reduced the tumor formation rate,total number of tumors,cancerous and non-cancerous tumors,tumor volume,ascites formation,and aberrant crypt foci count.At week 20,all three doses of EGCG were effective.Seventy-eight collective targets of EGCG and CRC were identified,of which 28 genes were dysregulated in CRC.Kyoto Encyclopedia of Genes and Genomes and GO analyses showed that the dysregulated genes were enriched in hsa05210(CRC),hsa04115(p53 signaling pathway),and hsa04151(PI3K-Akt signaling pathway),GO:0043124(negative regulation of I-kappaB kinase/NF-kappaB signaling pathway),GO:0043409(negative regulation of mitogen-activated protein kinase cascade),and GO:2001244(positive regulation of intrinsic apoptotic signaling pathway)respectively.CONCLUSION EGCG inhibits the formation of DMH-induced CRC by regulating key pathways involved in tumorigen

关 键 词：EPIGALLOCATECHIN gallate DIMETHYLHYDRAZINE Colorectal CANCER Aberrant CRYPT FOCI MITOGEN-ACTIVATED protein kinase The CANCER Genome Atlas 

分 类 号：R285[医药卫生—中药学]