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The Study To Explore Rhizoma Polygonati Polysaccharide On Cancer By Immune Regulation Based On TLR4-MAPK/NF-?B Signaling Pathways

Posted on:2019-06-21Degree:MasterType:Thesis
Country:ChinaCandidate:T T LongFull Text:PDF
GTID:2394330566982409Subject:Clinical Laboratory Science
Abstract/Summary:PDF Full Text Request
To investigate the immunoregulatory anti-cancer activity of PSP and the underlying mechanism,bioinformatics analysis was used to identify the DEGs and enriched signaling pathways in lung cancer.GSE19804was obtained from the Gene Expression Omnibus(GEO)database for significance analysis.DAVID software,STRING and cytoscape software were used to attain the 1970 DEGs enriched in Biological Process,77KEGG pathways associated with lung cancer,among which Toll-like-receptor(TLR)pathway was an important one.Top10 hub nodes and top 3 significant biological modules were identified from PPI network.Then,we investigated the effects and mechanisms of PSP on LLC,RAW264.7 and LLC tumor-bearing mice.CCK-8 assay was used for cell viability test and the results show the anti-cancer effect of PSP invitro,which was conincide with the inhibition of PSP on tumor growth in tumor-bearing mice.Immune organ indexes and CD4~+/CD8~+lymphocytes tested by Flow cytometry suggested PSP can enhance immune responses.Griess reaction and ELISA assays showed that the concentrations of NO and cytokines were increased by PSP.However,these effects were suppressed by TAK242 or ST2825 in vitro.The results of qRT-PCR and Western blot demonstrated that the mRNA and protein expressions of the critical nodes in the TLR4-MAPK/NF-?B signaling pathways(except TRAM)significantly increased after treatment with PSP not only in RAW264.7 but also in the spleen of tumor-bearing mice,suggested PSP exerts anti-cancer activity may be mediated by TLR4-MAPK/NF-?B signaling pathways,especially MyD88-dependent signaling pathway.
Keywords/Search Tags:Polygonatum sibiricum polysaccharides, TLR4, lung cancer, Immunomodulatory, bioinformatics
PDF Full Text Request
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