关键词: 肺癌, 异丙酚, 糖酵解, 葡萄糖转运体4

Abstract: Objective The Objective of this study was to investigate the effects of propofol on glycolysis of lung cancer,and to further explore its potential mechanism of inhibiting glycolysis in lung cancer through glucose transporter 4(GLUT4). Methods Human lung cancer A549 cells and mouse lung cancer LLC cells were cultured,and the experimental groups were set as the blank control group(Control group)and propofol(10 μmol/L)group(Propofol group).The CCK-8 assay was used to detect cell viability;Immunofluorescence(IF)was used to detect the expression of Ki-67 in lung cancer cells and A549 cell xenografts.Extracellular acidification rate(ECAR)and mitochondrial oxygen consumption(OCR)assays were used to detect the cellular metabolic levels;ELISA was used to detect the cell lactate and pyruvate content;Molecular docking experiments were used to detect the binding ability of GLUT4 with propofol using CB-Dock online tool;The glucose uptake kit was used to detect glucose uptake;Western blot was used to detect the expression of GLUT4,HK2,and PFK1 proteins in lung cancer cells. Results The cell viability of A549 cells(0.661±0.052)and LLC cells(0.632±0.033)in the propofol group was significantly inhibited by 10 μmol/L of propofol in lung cancer cells(P＜0.001).Compared with the control group,the average fluorescence intensity of Ki-67 in A549 and LLC positive cells(0.663±0.064 and 0.540±0.070)was significantly suppressed(P＜0.001).The ELISA results showed that compared with the control group,the levels of lactate and pyruvate in the propofol group decreased(P＜0.001),and under the action of propofol,the glucose uptake ability of cells decreased(P＜0.001).Molecular docking experiments using the CB-Dock online tool showed that GLUT4 had the strongest binding force with propofol.The results of Western blot showed a decrease in the expression of GLUT4 and its downstream HK2 and PFK1 proteins.After transient transfection and knockdown of GLUT4,cellular lactate(P＜0.001)and pyruvate content(P＜0.01)decreased,glucose uptake capacity reduced,and the inhibitory effect of propofol on glycolysis disappeared.In A549 cell xenografts,the weight of xenografts in the propofol group was significantly smaller than that of the model group(P＜0.001).Compared with the model group,the lactate content and pyruvate content decreased in the propofol group(P＜0.001). Conclusion Propofol can inhibit the proliferation of lung cancer cells and the progression of A549 cell xenografts in bearing mice by inhibiting the glycolysis of lung cancer cells,and its mechanism may be related to the targeted effect of GLUT4 on the glycolysis of lung cancer cells.

Key words: Lung cancer, Propofol, Glycolysis, Glucose transporter 4