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On The Mechanism Of Allicin And Resveratrol In Colorectal Cancer Cells

Posted on:2015-08-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:J HuangFull Text:PDF
GTID:1224330470466190Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective:The purpose is to study the molecular mechanism of antioxidants inhibiting the proliferation of human colorectal carcinoma cells by constructing gene expression profiles of colorectal cancer cells HCT116 and HT29 in differential expression, which were treated by the antioxidants of resveratrol and allicin, and by analysising the similarities and differences of gene expression of cancer cells treated by diverse antioxidants.Methods:We choose plant antioxidants:as candidates for research, with celecoxib as contrast, to study the function mechanism of resveratrol and allicin on the cells of colorectal cancer. We confirm IC50 by MIT and use it as antioxidant treat concentration. We used Illumina/Solexa, the high throughput sequencing to elucidate the anticarcinogenic mechanism of antioxidant on two colorectal cancer cell lines. With HiSeq2000 transcriptome sequencing, we sequence the cancer cells before and after the antioxidant treatment, find the difference of their gene expressions, and analyze the molecular mechanism of antioxidants inhibiting the proliferation of cancer cells by GO assement and PATHWAY analysis.Results:After the treatment with resveratrol and allicin, overexpressing genes found in two colorectal cancer cells are IL8, CXCL1, CXCL2, MT1X, MT1XP1, MT1P2, MT2A, RELB, BIRC3, CDA, RCAN1 and SERTAD1. After the colorectal cancer cells HCT116 and HT29 are treated with resveratrol and celecoxib, those genes related to ROS are up-regulated in two cancer cell lines.The co-regulated genes GO analysis suggests that chemokine receptor binding activity and chemokine GO are enriched in two cancer cell lines treated with three antioxidants. We use three kinds of antioxidants:resveratrol, allicin and celecoxib to respectively treat the transcriptomes of two colorectal cancer cells HCT116 and HT29, and find that co-regulated genes take part in the response to stimulus, signal transduction, cellular response to stimulus and GO by GO and PATHWAY analysis and three pathways take part in the antioxidant responses:Porphyrin and chlorophyll metabolism, Cytokine-cytokine receptor interaction, NF-kappa B signaling pathway. In addition, by comparing the transcriptomes of two colorectal cancer cells treated with the same antioxidant, we analyze GO and PATHWAY with co-regulated genes took part in and find these genes also take part in Apoptotic, ROS, Chemokine. These con-regulated genes take part in three pathways:NF-kappa B signaling pathway, NOD-like receptor signaling pathway and Legionellosis. The real-time quantitative verifys that the expression quantities of genes in NF--kappa B signaling pathway are markedly changed before and after the treatment.Conclusion:By comparing the transcriptomes of two colorectal cancer cells respectively treated with three kinds of antioxidants:resveratrol, allicin and celecoxib, we find the expression quantities of genes in NF--kappa B signaling pathway are markedly changed before and after the treatment. The antioxidant may inhibit colon cancer cells mainly by NF--kappa B signaling pathway.
Keywords/Search Tags:colorectal cancers, ROS, RNA-seq, Resveratrol, Allicin, Antioxidants
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