Cytoplasmic M‑CSF facilitates apoptosis resistance by inhibiting the HIF‑1α/BNIP3/Bax signalling pathway in MCF‑7 cells

Abstract

Macrophage colony-stimulating factor (M-CSF), a tumour marker, is related to tumour cell anti-apoptosis and drug resistance. However, the role of M-CSF in MCF-7 cells is unknown. In the present study, the effect and mechanism of M-CSF on hypoxia-inducible factor-1α (HIF-1α)/BCL2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)/Apoptosis Regulator BAX signalling in human breast cancer MCF-7 cells were investigated. Western blotting revealed that the expression of HIF-1α, BNIP3, Bax, caspase-3 and caspase-9 was lower in MCF-7-M cells compared to MCF-7 and MCF-7-C cells treated with adriamycin (ADM). Immunoprecipitation combined with western blotting was used to detect the interaction between Bcl-2 and BNIP3 or Bax protein. MCF-7-M cells had a higher amount of Bax binding to Bcl-2 compared to MCF-7 cells or MCF-7-C cells, while the amount of BNIP3 binding to Bcl-2 was decreased in MCF-7-M cells. Hoechst 33342 staining and flow cytometry were utilized to evaluate the effect of M-CSF on apoptosis in MCF-7 cells treated with ADM. Compared to ADM-treated MCF-7 cells, the apoptotic rate of MCF-7-M cells was significantly decreased. These effects were dependent on the concentration of ADM. In conclusion, cytoplasmic M-CSF suppressed apoptosis by inhibiting the HIF-1α/BNIP3/Bax signalling pathway, which potentiated the dissociation of Bcl-2 from Bcl-2-BNIP3 compounds and the formation of Bcl-2-Bax compounds.

HNF4α overexpression enhances the therapeutic potential of umbilical cord mesenchymal stem/stromal cells in mice with acute liver failure

“…We confirmed the anti-apoptotic effect of HB-EGF secreted by HNF4a-hUMSCs [25]. Among these, macrophage colony-stimulating factor (M-CSF), a tumour marker, was also related to tumour cell antiapoptosis [45]. More surprisingly, MSC-exosomes have shown an anti-apoptotic effect on hepatocytes in LPS/ D-GalN-induced acute liver injury, along with the downregulation of cleaved caspase-3 [46].…”

Comprehensive analysis of the expression and significance of CXCLs in human diffuse large B-cell lymphoma

“…They might be related to apoptosis. Fas, IFN-γ, COX2, CSF, TRAIL and so on can induce or promote apoptosis (KEGG) 41 – 45 . We can further explore the expression of CXCLs and their mechanism of apoptosis in DLBCL.…”

Chemotherapeutics and CAR‐T Cell‐Based Immunotherapeutics Screening on a 3D Bioprinted Vascularized Breast Tumor Model

“…[43] Increased expression of all these factors enables the cancer cells to evade drug-induced death. [44,45] Cellular engineering of immune cells as CAR-T cells has shown great therapeutic promise against hematological tumors but is not yet effective against solid tumors. An immunesuppressive microenvironment composed of a dense mass of tumor and stromal cells and abnormal vasculature restricts immune cell infiltration and thus suppresses immune function.…”

“…[ 43 ] Increased expression of all these factors enables the cancer cells to evade drug‐induced death. [ 44,45 ]…”