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Glycine Metabolomics Study On Cancer Cells And Its Intervention Of Drugs With LC-MS

Posted on:2018-10-03Degree:MasterType:Thesis
Country:ChinaCandidate:X X ZhouFull Text:PDF
GTID:2404330518482963Subject:Medicinal chemistry
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Now,it has been found that glycine and glycine decarboxylase are associated with the occurrence and development of cancer.So we studied the glycine metabolomics of several cancer cells and its intervention effects of drugs with LC-MS in this research.We first identified the glycine metabolites and analyzed the data of metabolites samples through PCA and OPLS-DA methods;then screened the differential metabolites of glycine and analyzed their metabolism pathway;at last summarizedthe intervention effect of drugs on glycine metabolites in different cells.The main research results are as follows:(1)Study the intervention effect of drugs on glycine metabolites in A549 cells:The intervention effect of drugs on glycine metabolits are mainly in Glycine-Serine-Threonine metabolism pathway,Cysteine-Methionine and Purine metabolism pathway;It is also found that 5'-Phosphoribosylglycinamide(9)was downregulated in A549 cells treated with different drugs.It implys the compound 9 may be a potential biomarker for screening anticancer drugs.(2)Study the intervention effect of Gefitinib(targeted EGFR)and Afatinib(targeted EGFR&HER2)on glycine metabolites in A549 cellsand H1299 cells(lack of p53):It's found that the HER2 genes have influence on glycine metabolites and the lack of p53 increase the sensitivity of glycine metabolites to anti-cancer drugs in cancer cells.(3)Study the intervention effect of SAHA and LP01on glycine metabolitesin A549 cells and Hella cells:LP01 has similar intervention effect with SAHA whether in A549 cells or Hela cells,it indicats that LP01 may have the same anti-cancer machenism with SAHA which has been initially verified by Western Blot assay.These results provide a scientific basis for building model to screening potential anti-cancer drug through cell metabolomics.All together,these findings set the preliminary stage for the anti-cancer targeting drug screening model based on cell metabolomics,and may help exploring the target for cancer intervention treatment.
Keywords/Search Tags:Glyicine metabolites, Metabolomics, LC-MS
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