The Role And Mechanism Of Bim In Inhibiting The Apoptosis Of Breast Cancer MCF-7 Cell Line By M-CSF

Objective: To investigate the effect of cytoplasmic macrophage colony stimulating factor(M-CSF) on the apoptosis of human breast cancer cell line MCF-7 and the role of PI3K/Akt/FoxO3 a signaling pathway in it.Methods: MCF-7 cell line stably transfected with M-CSF cell line was used as the research object.Western Blotting was detected the expression of M-CSF, MST1, Bim and PI3K/Akt/FoxO3 a signaling pathway protein. Hoechst33258 staining and flow cytometry were used to detect the apoptosis rate of the cells. And the subcellular localization of FoxO3 a were detected by immunofluorescence and Western blotting.Result:1.Cytosolic M-CSF down-regulates the expression of Bim and MST1 in MCF-7 cells(p<0.05).Cytoplasmic M-CSF can decrease the apoptosis rate of MCF-7 cells.2.Cytoplasmic M-CSF down-regulates the expression of nuclear FoxO3a(p<0.05),and up-regulates the expression of cytoplasmic FoxO3a(p<0.05), and promotes the translocation of FoxO3 a to the cytoplasm.3.Cytosolic M-CSF up-regulates the expression p-MST1, p-FoxO3a(p<0.05), and down-regulates the expression of MST1, Bim(p<0.05) in MCF-7 cells.LY294002,the inhibitor of PI3 K reverses the down-regulation of Bim and MST1 induced by M-CSF(p<0.05), and promotes the translocation of FoxO3 a to nucleus.4. MST1-si RNA silences the expression of MST1, promotes phosphorylation of FoxO3 a S253(p<0.05) and further down-regulate the expression of Bim(p<0.05).Conclusion:1.Cytoplasmic M-CSF inhibits the apoptosis of breast cancer MCF-7 cells by down-regulating the expression of Bim.2. The nuclear and internal migrating of FoxO3 a protein is one of the molecular basis of cell apoptosis.3. The cytoplasmic M-CSF down-regulates the expression of Bim by activating the PI3K/Akt/FoxO3 a signaling pathway to inhibit the apoptosis of breast cancer MCF-7 cells. The PI3K/Akt/MST1 pathway may play a role in the down-regulation of Bim expression.