Published online May 7, 2020. doi: 10.3748/wjg.v26.i17.2064
Peer-review started: November 20, 2019
First decision: January 7, 2020
Revised: February 13, 2020
Accepted: March 11, 2020
Article in press: March 11, 2020
Published online: May 7, 2020
Processing time: 168 Days and 14.4 Hours
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.
To understand the inhibitory mechanisms of EGCG on CRC cell proliferation and identify its pharmacological targets by network pharmacology analysis.
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.
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.
EGCG inhibits the formation of DMH-induced CRC by regulating key pathways involved in tumorigenesis.
Core tip: Our research found that epigallocatechin gallate (EGCG) extracted from tea can inhibit the occurrence of colorectal cancer (CRC) in dimethylhydrazine-induced rat models and predicted the interaction between EGCG and CRC target genes using a bioinformatics database. The Cancer Genome Atlas database was used to further explore the significant differences of 28 genes among 78 intersection target genes and Kyoto Encyclopedia of Genes and Genomes and Gene ontology analyses were performed to explore the pathway and mechanism of EGCG on CRC.