Lung cancer is the most common primary malignant lung tumor. However, the etiology of lung cancer is still unclear. Fatty acids include short-chain fatty acids (SCFAs) and polyunsaturated fatty acids (PUFAs) as essential components of lipids. SCFAs can enter the nucleus of cancer cells, inhibit histone deacetylase activity, and upregulate histone acetylation and crotonylation. Meanwhile, PUFAs can inhibit lung cancer cells. Moreover, they also play an essential role in inhibiting migration and invasion. However, the mechanisms and different effects of SCFAs and PUFAs on lung cancer remain unclear. Sodium acetate, butyrate, linoleic acid, and linolenic acid were selected to treat H460 lung cancer cells. Through untargeted metabonomics, it was observed that the differential metabolites were concentrated in energy metabolites, phospholipids, and bile acids. Then, targeted metabonomics was conducted for these three target types. Three LC-MS/MS methods were established for 71 compounds, including energy metabolites, phospholipids, and bile acids. The subsequent methodology validation results were used to verify the validity of the method. The targeted metabonomics results show that, in H460 lung cancer cells incubated with linolenic acid and linoleic acid, while the content of PCs increased significantly, the content of Lyso PCs decreased significantly. This demonstrates that there are significant changes in LCAT content before and after administration. Through subsequent WB and RT-PCR experiments, the result was verified. We demonstrated a substantial metabolic disparity between the dosing and control groups, further verifying the reliability of the method.
The important metabolic characteristics of cancer cells include increased fat production and changes in amino acid metabolism. Based on the category of tumor, tumor cells are capable of synthesizing as much as 95% of saturated and monounsaturated fatty acids through de novo synthesis, even in the presence of sufficient dietary lipid intake. This fat transformation starts early when cell cancerization and further spread along with the tumor cells grow more malignant. In addition, local catabolism of tryptophan, a common feature, can weaken anti-tumor immunity in primary tumor lesions and TDLN. Arginine catabolism is likewise related with the inhibition of anti-tumor immunity. Due to the crucial role of amino acids in tumor growth, increasing tryptophan along with arginine catabolism will promote tumor growth. However, immune cells also require amino acids to expand and distinguish into effector cells that can kill tumor cells. Therefore, it is necessary to have a deeper understanding of the metabolism of amino acids and fatty acids within cells. In this study, we established a method for the simultaneous analysis of 64 metabolites consisting of fatty acids and amino acids, covering biosynthesis of unsaturated fatty acids, aminoacyl-tRNA biosynthesis, and fatty acid biosynthesis using the Agilent GC-MS system. We selected linoleic acid, linolenic acid, sodium acetate, and sodium butyrate to treat H460 cells to validate the current method. The differential metabolites observed in the four fatty acid groups in comparison with the control group indicate the metabolic effects of various fatty acids on H460 cells. These differential metabolites could potentially become biomarkers for the early diagnosis of lung cancer.
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