Abstract: Objective: To investigate the effects of macrophage stimulating 1 receptor(MSTIR) inhibitor BMS777607 on the proliferation and apoptosis of lung cancer A549 cells, and to clarify their possible mechanisms. Methods: The A549 cells of human lung cancer were selected and treated with BMS777607 at different concentrations (1, 5, 10, 15,and 20 μmol·L^-1) for 48 h;at the same time,control group was set up.The proliferation rates of A549 cells in various groups were detected by MTT method.The A549 cells were treated with BMS777607 at different concentrations (1, 5, 10, 15,and 20 μmol·L^-1) for 14 d;at the same time,control group was set up.The colony formation of A549 cells in various groups were observed by colony formation experiment,and the proliferation rates of A549 cells were detected.The A549 cells were treated with different concentrations(10 and 20 μmol·L^-1) of BMS777607 for 24 h;at the same time,control group was set up.The number of EdU positive cells in various groups were detected by EdU incorporation method. The A549 cells were treated with BMS777607 at different concentrations (1, 5, 10, 15, 20μmol·L^-1) for 48 h;at the same time,control group was set up.The apoptotic rates were detected by flow cytometry.Western blotting method was used to detect the expression levels of protein kinase B(AKT),phosphorylated AKT (p-AKT), extracellular regulatory protein kinase(ERK),phosphorylated ERK(p-ERK), polyglycoside diphosphate ribose polymerase (PARP), Cleaved-PARP, Caspase 9 and Cleaved-Caspase 9. Results: The MTT assay results showed that compared with control group, the proliferation rates of A54 cells in different concentrations of BMS777607 groups were decreased significantly (P<0.05 or P<0.01) in a concentration and time dependent manner.In colony formation experiment,compared with control group,the number of colony formation of A549 cells in 10 μmol·L^-1 BMS777607 group was significantly decreased,and the colony formation almost was not found in 20 μmol·L^-1 BMS777607 group; compared with control group,the colony formation rates in different concentrations of BMS777607 groups were significantly decreased (P<0.05 or P<0.01).In experiment of EdU incorporation, the proliferation rates of A549 cells in 10 and 20 μmol·L^-1 BMS777607 groups were decreased significantly compared with control group (P<0.05 or P<0.01).The flow cytometry results showed that compared with control group, the apoptotic rates of A549 cells in 10, 15 and 20 μmol·L^-1BMS777607 groups were significantly increased (P<0.05).The results of Western blotting method showed that the expression levels of p-AKTand p-ERK proteins in the A549 cells in different concentrations of BMS777607 were significantly decreased(P<0.05), and the expression levels of Cleaved-PARP and Cleaved-Caspase 9 were significantly increased (P<0.05). Conclusion: MST1R inhibitor BMS777607 can inhibit the proliferation of lung cancer A549 cells and induce apoptosis,and its mechanism may be related to the inhibition of the expressions of p-AKT and p-ERK and the promotion of the expressions of PARP and Caspase 9.

Key words: macrophage stimulation 1 receptor, BMS777607, lung neoplasm, apoptosis, phosphorylated protein kinase B poly ADP-ribose polymerase