Effects Of MST1R Inhibitor BMS777607 On Proliferation And Apoptosis Of Lung Cancer A549 Cells

ObjectiveThis study investigated the effect of MST1R inhibitor BMS-777607 on the proliferation and apoptosis of lung adenocarcinoma cell line A549,and explored the possibility of MST1R as a potential clinical target for the treatment of non-small cell lung cancer.MethodsHuman lung adenocarcinoma A549 cells were treated with BMS-777607(1,5,10,15,20μmol·L^-1)at different concentrations for 48h,and the effect of BMS-777607 on cell proliferation was detected by MTT assay.A549 cells were treated with BMS-777607(1,5,10,15,20μmol·L^-1)at different concentrations for 14d,and the effect of BMS-777607 on cell proliferation was detected by cell cloning formation experiment.A549 cells were treated with BMS-777607(0,10,20μmol·L^-1)at different concentrations for 24h,and the effect of BMS-777607 on cell proliferation was detected by Ed U doping.The A549 cells were treated with different concentrations of BMS-777607(0,1,5,10,15,20μmol·L^-1)for 48h,and the effect of BMS-777607 on apoptosis was detected by flow cytometry.Western blotting was used to detect the effect of BMS-777607 on the expression levels of p-AKT,p-ERK,PARP and casepase9.ResultsIn this study,the effects of BMS-777607 on A549 cells were studied from the aspects of proliferation and apoptosis.1.Inhibition of cell proliferation:MTT results showed that the inhibition rate of BMS-777607 on the proliferation of A549 cells increased with the increase of drug concentration and the extension of action time.Compared with the control group(0μmol·L^-1),the inhibitory effect was the most obvious when the drug concentration was 10μmol·L^-1and the action time was 72h（P<0.01）.The results of cell clone formation experiments showed that BMS-777607significantly inhibited the clone formation of A549 cells,and the inhibition rate was positively correlated with the drug concentration（P<0.01）.The experimental results of Ed U incorporation showed that compared with the control group(0μmol·L^-1),the cell proliferation rate of the dosing group(10μmol·L^-1,20μmol·L^-1)significantly decreased（P<0.05 or P<0.01）.2.Promoting cell apoptosis:The results of double-staining flow cytometry showed that the apoptosis rate of the dosing group(1,5,10,15,20μmol·L^-1)increased with the drug concentration（P<0.05）.Western blot results showed that with the increase of BMS-777607,the expression levels of p-AKT and p-ERK gradually decreased（p<0.05）,while the expression levels of PARP and casepase9（p<0.05）gradually increased.ConclusionsMST1R inhibitor BMS-777607 can inhibit the proliferation of lung adenocarcinoma A549 cells and induce apoptosis,which may be related to the inhibition of the expressions of p-AKT and p-ERK and the promotion of the expressions of PARP and casepase9.