Conclusion
Our findings indicated anti-tumor effects of propofol on the lung cancer but not brain cancer, through the regulation of tumor metastasis-related genes, multi-cellular signaling and cellular metabolism.
Methods
The cell viability, proliferation, migration, and invasion of cancer cells were analyzed with CCK-8, Ki-67 staining, wound healing, and Transwell assay, respectively. The protein changes were analyzed with Western blot and immunofluorescent staining. The metabolomics alteration was studied with 1H-NMR spectroscopy. The gene expression regulations were analyzed with PCR gene array and qRT-PCR experiments.
Results
In this study, we found that propofol reduced cell viability and inhibited cell proliferation, migration and invasion of lung cancer cells, but not neuroglioma cells. In lung cancer cells, propofol downregulated glucose transporter 1 (GLUT1), mitochondrial pyruvate carrier 1 (MPC1), p-Akt, p-Erk1/2, and hypoxia- inducible factor 1 alpha (HIF-1 α ) expressions and upregulated pigment epithelium-derived factor (PEDF) expression. Propofol increased intracellular glutamate and glycine but decreased acetate and formate whilst increased glucose, lactate, glutamine, succinate, pyruvate, arginine, valine, isoleucine, and leucine and glycerol, and decreased acetate, ethanol, isopropanol in the culture media of lung cancer cells. Furthermore, VEGFA, CTBP1, CST7, CTSK, CXCL12, and CXCR4 gene expressions were downregulated, while NR4A3, RB1, NME1, MTSS1, NME4, SYK, APC, and FAT1 were upregulated following the propofol treatment. Consistent with the phenotypical changes, these molecular and metabolic changes were not found in the neuroglioma cells.