~1H Nmr Based Metabolomics Analysis Of Lung Adenocarcinoma

Objective In this study,A549 cell lines and A549 y cell lines have different grade malignancy.Afterward,we find some differences in biology traits between this two groups of cells,such as tumor proliferation and invasion.We applied NMR metabonomics study of A549 cell lines to find metabolic changes after genetic modification.Also,we seeked the links between gene level and metabolic level so that combined with genomics,transcriptomics,proteomics and metabolomics,and established the position of metabolomics in the research of malignancy.Methods In this work,we used lentiviral vector techniques to construct stably transfected cell lines of A549y;What’s more,we applied MTT assay to test cell proliferation and used TUNEL assay to cell apoptosis;In addition,we performed NMR metabolomic analysis of the lung cancer cell line A549 and alpha(1,3)GT-A549.Pattern recognition methods(PCA,PLS-DA and OPLS-DA)were used to screening different metabolites in these samples.We discovered that this two groups showed distinct metabolic profiles with clearly discrepant levels of different metabolites.HMDB and KEGG databases were applied to determine discrepant metabolic pathways.Results The first part of this study we found that the A549 y cell lines showed the higher cellular morphology and proliferation rates than normal A549 cells.In the second part,we applied NMR metabolomic analysis and pattern recognition to identify sixteen kinds of discrepant metabolites,such as fatty acids,isoleucine/ leucine,lactic acid,alanine,L-cysteine,glutaric,glutamine,lysine,arginine,taurine,histidine,glucose,glycine,glycerol,creatine phosphate,ATP.Meanwhile,According to Metabo Analyst 3.0 system,we fixed that two groups of cells have differences in metabolic pathways of arginine metabolism and lysine degradation.Conclusion These results show that Genetic modification,changing the energy supply system of the tumor cells,can enhance the features of intracellular aerobic glycolysis;The increase of histamine synthesis was an active action of tumor cell proliferation;The lock of phosphocreatine can endogenous cells lack the ability of "self-limiting growth";In addition,Low concentrations of arginine generated low concentrations of NO by arginine metabolic pathways,which may promote tumor growth.