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

Zhang,Mengxia; Liu,Qi; Li,Lijun; Ning,Jing; Tu,Jian; Lei,Xiaoyong; Mo,Zhongcheng; Tang,Shengsong

doi:10.3892/or.2018.6949

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

Authors:
- Mengxia Zhang
- Qi Liu
- Lijun Li
- Jing Ning
- Jian Tu
- Xiaoyong Lei
- Zhongcheng Mo
- Shengsong Tang
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Affiliations: Department of Histology and Embryology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P.R. China, Clinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, University of South China, Hengyang, Hunan 421001, P.R. China, Insitute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan 421001, P.R. China, Department of Pharmacology, Hunan University of Medicine, Huaihua, Hunan 418000, P.R. China, Hunan Province Key Laboratory for Antibody-based Drug and Intelligent Delivery System, Hunan University of Medicine, Huaihua, Hunan 418000, P.R. China
Published online on: December 21, 2018 https://doi.org/10.3892/or.2018.6949
Pages: 1807-1816

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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.

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