Abstract: Objective: To investigate the effects of macrophage stimulating 1 receptor (MST1R) inhibitor BMS-777607 on the proliferation and apoptosis of the breast cancer MCF-7 cells, and to elucidate the mechanisms. Methods: The breast cancer MCF-7 cells treated with different concentrations of BMS777607 were divided into control group (0μmol·L^-1 BMS-777607 group) and 0.5,1.0,2.0,5.0,10.0,15.0,and 20.0μmol·L^-1 BMS-777607 groups. MTT method was used to detect the proliferation rates of the MCF-7 cells in various groups, and clone formation assay was used to detect the survival rates of the MCF-7 cells in various groups; EDU imaging and EDU flow cytometry methods were used to detect the proliferation rates of the MCF-7 cells in various groups,and Hoechst33342 staining was used to detect the apoptotic morphology of the MCF-7 cells in various groups; flow cytometry was used to detect the apoptotic rates of the MCF-7 cells in various groups,and Western blotting method was used to detect the expression levels of ERK,p-ERK, Akt,p-Akt, PARP,Cleaved PARP, Bax, Caspase-3,Cleaved Caspase-3,Caspase-9 and Cleaved Caspase-9 proteins in the MCF-7 cells in various groups. Results: The MTT results showed that compared with control group, the proliferation rates of the MCF-7 cells in 5 and 10μmol·L^-1 BMS-777607 groups were increased (P<0.05 or P<0.01). The clone formation assay results showed that compared with control group, the survival rates of the MCF-7 cells in 5 and 20μmol·L^-1 BMS-777607 groups were increased (P<0.05 or P<0.01).The EDU incorporation results showed that compared with control group, the proliferation rates of the MCF-7 cells in 10 and 20μmol·L^-1 BMS-777607 groups were increased (P<0.05 or P<0.01).The Hoechst33342 fluorescence staining results showed that the MCF-7 cells in control group showed the light staining, a small number of MCF-7 cells in 10μmol·L^-1 BMS-777607 group showed the bright nuclei,and most of the MCF-7 cells in 20μmol·L^-1 BMS-777607 group showed the bright nuclei. The flow cytometry results showed that compared with control group, the apoptotic rates of the MCF-7 cells in 10 and 20μmol·L^-1 BMS-777607 groups were decreased (P<0.05). The Western blotting results showed that compared with control group, the expression levels of p-ERK and p-Akt proteins in the MCF-7 cells in 10, 15, and 20μmol·L^-1BMS-777607 groups were significantly decreased(P<0.05 or P<0.01), and the expression levels of PARP, Cleaved PARP, Bax, Cleaved Caspase-3, and Cleaved Caspase-9 proteins were significantly increased(P<0.05 or P<0.01). Conclusion: MST1R inhibitor BMS777607 can inhibit the proliferation of MCF-7 cells and induce the apoptosis, and their mechanisms are related to the inhibition of p-ERK and p-Akt expressions and the promotion of expressions of Cleaved PARP, Bax, Cleaved Caspase-9 and Cleaved Caspase-3.

Key words: BMS-777607, breast neoplasms, cell proliferation, apoptosis, macrophage stimulating 1 receptor