Effect Of MST1R Inhibitor BMS-777607 On Proliferation And Apoptosis Of Breast Cancer MCF-7 Cells

ObjectiveTo investigate the effect of MST1R（Macrophage Stimulating 1 Receptor）inhibitor BMS-777607 on proliferation and apoptosis of breast cancer（BC）MCF-7 cells.In order to provide the experimental basis for clinical targeted treatment of breast cancer in the future.MethodsMCF-7 cells were treated with different concentrations of BMS-777607（0.5,1,2,5,10,15,20μmol·L-1）which were cultured in vitro,and set up a control group（DMSO）.MTT experiments was used to detect the proliferation rate of MCF-7 cells in each group.Colony experiments was used to detect the cell viability of MCF-7 cells in each group.Ed U incorporation was used to detect cellular DNA replication activity.Hoechst 33342 fluorescence staining was used to detect the nuclear condensation and chromatin aggregation.Flow cytometry was used to analyze the apoptosis of each group.Western blotting was used to detect the protein expression of PARP,Bax,Caspase9,Caspase3,ERK,Akt in each group.ResultsThe results of MTT experiments,colony experiments,and Ed U incorporation showed that compared with the control group,the viability of MCF-7 cells in the medicated group was significantly reduced,and was time-dependent and concentration-dependent（P<0.05）.Hoechst 33342fluorescence staining experiments showed that the control group had lightly stained nuclei,the medicated group had thick,bright nuclei,and chromatin was condensed.Flow cytometry experiment showed that compared with the control group,the apoptosis rate of MCF-7 cells in the medicated group increased significantly with increasing concentration（P<0.05）.Western blotting results showed that compared with the control group,the expression levels of PARP,Bax,Cleaved-Caspase9,and Cleaved-Caspase3 proteins in MCF-7 cells increased significantly with increasing inhibitor concentrations（P<0.05）.However,p-Akt,p-ERK protein expression level was significantly reduced（P<0.05）.ConclusionsMST1R inhibitor BMS-777607 can inhibit the proliferation and induce apoptosis of breast cancer MCF-7 cell at the concentration of 5μmol·L^-1～20μmol·L^-1,which may be related to inhibiting the expression of p-ERK and p-Akt and promoting the expression of PARP,Bax,Cleaved-Caspase9,and Cleaved-Caspase3.