| Summary: | 碩士 === 國立成功大學 === 化學系碩博士班 === 96 === Proteomics is a class of science developed from genomics. Identification, localization, and functionalization of every kind of proteins and protein interactions in cells are focused. Thus, proteomics can be applied for characterizing drug interactions and for establishing bioinformatics.
In this article, we used tandem MS and stable isotope dimethyl labeling to investigate the effects of compound 1250 on lung cancer cells (Lung Adenocarcinoma A549). In order to examine nuclear proteins that are related to the survival and apoptosis of cancer cells, we focused on the quantification for nuclear proteome.We attempted new nuclear extraction method that increases the number of identified nuclear proteins by 3.7 times. The lysate of nuclear extract with and without the treatment of compound 1250 were labeled with H2-formaldehyde and D2-formaldehyde, respectively, in order to profile the protein amount in two conditions. Base on the results of proteome analysis and bioassays, it was found that the amount of PA2G4 was increased 1.6 time upon the treatment of compound 1250 treatment. Such increase was believed to be related to cell apoptosis via PI3/Akt and Akt phosphorylation pathway. The activation of Akt inhibits cell apoptosis and promotes cell survival. From the results, we propose that compound 1250 encourages cell survival. Under a high concentration (150 ng/ml) of Vascular endothelial growth factor C (VEGFC), compound 1250 inhibits cell proliferation by reducing cell accumulation in G1/S phase. Such inhibition may be related to VEGFR3 pathway but not PA2G4.
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