title: Doxorubicin resistance mediated by cytoplasmic macrophage colony-stimulating factor is associated with switch from apoptosis to autophagic cell death in MCF-7 breast cancer cells.
abstract: Macrophage colony-stimulating factor is a vital factor in maintaining the biological function of monocyte-macrophage lineage. It is expressed in many tumor tissues and cancer cells. Recent findings indicate that macrophage colony-stimulating factor might contribute to chemoresistance, but the precise mechanisms are unclear. This study was to explore the effect of macrophage colony-stimulating factor on doxorubicin resistance in MCF-7 breast cancer cells and the possible mechanism. In the study, the human breast cancer cells, MCF-7, were transfected with macrophage colony-stimulating factor. We document that cytoplasmic macrophage colony-stimulating factor induces doxorubicin resistance and inhibits apoptosis in MCF-7 cells. Further studies demonstrated that cytoplasmic macrophage colony-stimulating factor-mediated apoptosis inhibition was dependent on the activation of PI3K/Akt/Survivin pathway. More importantly, we found that macrophage colony-stimulating factor-induced autophagic cell death in doxorubicin-treated MCF-7 cells. Taken together, we show for the first time that macrophage colony-stimulating factor-induced doxorubicin resistance is associated with the changes in cell death response with defective apoptosis and promotion of autophagic cell death.
authors.affiliation: 1 Biomedical Research Center, Hunan University of Medicine, Huaihua 418000, China.|2 Department of Histology and Embryology, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China.
authors.forename: Mengxia
authors.initials: M
authors.lastname: Zhang
authors.affiliation: 2 Department of Histology and Embryology, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 2 Department of Histology and Embryology, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Tang
authors.affiliation: 2 Department of Histology and Embryology, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 2 Department of Histology and Embryology, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China.
authors.forename: Zhongcheng
authors.initials: Z
authors.lastname: Mo
authors.affiliation: 2 Department of Histology and Embryology, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Lei
authors.affiliation: 1 Biomedical Research Center, Hunan University of Medicine, Huaihua 418000, China.|2 Department of Histology and Embryology, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China.
authors.forename: Shengsong
authors.initials: S
authors.lastname: Tang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects* / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D016173:Macrophage Colony-Stimulating Factor
keywords: Macrophage colony-stimulating factor; apoptosis; autophagy; breast cancer; chemoresistance