AIM To investigate the chemopreventiveeffects of green tea and tea pigment on 1,2-dimethylhydrazine(DMH)-induced rat colorectalcarcinogenesis.METHODS Male weaning Wistar rats wererandomly allocated into four groups.Ra...AIM To investigate the chemopreventiveeffects of green tea and tea pigment on 1,2-dimethylhydrazine(DMH)-induced rat colorectalcarcinogenesis.METHODS Male weaning Wistar rats wererandomly allocated into four groups.Rats in thepositive control group were given s.c.injectionof DMH,once a week for ten weeks;rats in tea-treated groups,with the same DMH treatment asin the positive group,received 2% green tea and0.1% tea pigments;rats in the negative controlgroup were given s.c.injection of the samevolume of saline as well as DMH in the positivegroup.Animals were sacrified and necropsied atthe end of week 16 and week 32.RESULTS Aberrant cryptic foci(ACF)wereformed in animals in DMH-treated groups at theend of week 16.Compared to the DMH group,green tea and tea pigments groups had less ACF(148.25 and 204.25,respectively,P【0.01).Atthe end of week 32,all rats in DMH groupdeveloped large intestinal tumors.The resultsalso showed that DMH increased labeling index(LI)of proliferating cell nuclear antigen(PCNA)of intestinal mucosa and the expression of ras-p21.However,in the tea-treated groups,PCNA-LI was significantly reduced as compared withthe positive control group(36.63 and 40.36 inthe green tea group and tea pigment group,respectively,at the end of the experiment,P【0.01).ras-p21 expression was alsosignificantly reduced(2.07 and 2.36 in the colontumors of rats in the green tea group and teapigments group,respectively at the end of theexperiment,P【0.01).Furthermore,green tea and tea pigment inhibited the expression of Bcl-2protein(2,5,1,0 and 2,4,1,0,respectively,at the end of the experiment P【0.01),andinduced expression of Bax protein(0,1,3,4and 0,1,4,3,respectively,P【0.01).CONCLUSION Chinese green tea drinkinginhibited ACF and colonic tumors formation inrats,which showed that tea had a significantchemopreventive effect on DMH-inducedcolorectal carcinogenesis.Such effects may bedue to suppression of cell proliferation andinduction of apoptosis in the intestinal crypts.展开更多
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(...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 tumorigenesis.展开更多
文摘AIM To investigate the chemopreventiveeffects of green tea and tea pigment on 1,2-dimethylhydrazine(DMH)-induced rat colorectalcarcinogenesis.METHODS Male weaning Wistar rats wererandomly allocated into four groups.Rats in thepositive control group were given s.c.injectionof DMH,once a week for ten weeks;rats in tea-treated groups,with the same DMH treatment asin the positive group,received 2% green tea and0.1% tea pigments;rats in the negative controlgroup were given s.c.injection of the samevolume of saline as well as DMH in the positivegroup.Animals were sacrified and necropsied atthe end of week 16 and week 32.RESULTS Aberrant cryptic foci(ACF)wereformed in animals in DMH-treated groups at theend of week 16.Compared to the DMH group,green tea and tea pigments groups had less ACF(148.25 and 204.25,respectively,P【0.01).Atthe end of week 32,all rats in DMH groupdeveloped large intestinal tumors.The resultsalso showed that DMH increased labeling index(LI)of proliferating cell nuclear antigen(PCNA)of intestinal mucosa and the expression of ras-p21.However,in the tea-treated groups,PCNA-LI was significantly reduced as compared withthe positive control group(36.63 and 40.36 inthe green tea group and tea pigment group,respectively,at the end of the experiment,P【0.01).ras-p21 expression was alsosignificantly reduced(2.07 and 2.36 in the colontumors of rats in the green tea group and teapigments group,respectively at the end of theexperiment,P【0.01).Furthermore,green tea and tea pigment inhibited the expression of Bcl-2protein(2,5,1,0 and 2,4,1,0,respectively,at the end of the experiment P【0.01),andinduced expression of Bax protein(0,1,3,4and 0,1,4,3,respectively,P【0.01).CONCLUSION Chinese green tea drinkinginhibited ACF and colonic tumors formation inrats,which showed that tea had a significantchemopreventive effect on DMH-inducedcolorectal carcinogenesis.Such effects may bedue to suppression of cell proliferation andinduction of apoptosis in the intestinal crypts.
基金Supported by Nursing Advantage Discipline Construction Project Foundation of Jiangsu Province University,No.2019YSHL107Nanjing Medical Science and Technique Development Foundation,No.NWQR-201705.
文摘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 tumorigenesis.
