title: BMP4 is involved in the chemoresistance of myeloid leukemia cells through regulating autophagy-apoptosis balance.
abstract: This study showed that silencing BMP4 expression significantly activated caspase-2, 3, and 9, while decreasing Matrigel colony formation in Cytarabine (Ara-C)-treated leukemia HL-60 cells. In contrast, Ara-C significantly upregulated Atg5 and Beclin-1 expression, the ratio of LC3-II/LC3-I, and CDK1 and cyclin B1 expression in leukemia cells expressing BMP4. BafA significantly sensitized the apoptotic effect of Ara-C in leukemia cells. Injection of Ara-C significantly inhibited tumor growth in mice inoculated with leukemia cells with BMP4 silenced. In conclusion, BMP4 plays a crucial role in the chemoresistance of leukemia cells through the activation of autophagy and subsequent inhibition of apoptosis.
authors.affiliation: 1Department of Hematology, Xiangya Hospital.
authors.forename: Xielan
authors.initials: X
authors.lastname: Zhao
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Minyuan
authors.initials: M
authors.lastname: Peng
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Fangping
authors.initials: F
authors.lastname: Chen
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000096:biosynthesis; D053143:Caspase 2 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000096:biosynthesis; D003561:Cytarabine / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000503:physiopathology*; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D009368:Neoplasm Transplantation; D034622:RNA Interference; D034741:RNA, Small Interfering; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: C502778:ATG5 protein, human; D000964:Antimetabolites, Antineoplastic; D051017:Apoptosis Regulatory Proteins; D000071187:Autophagy-Related Protein 5; C491997:BECN1 protein, human; C525809:BMP4 protein, human; D000071186:Beclin-1; D055415:Bone Morphogenetic Protein 4; C534699:CCNB1 protein, human; D056744:Cyclin B1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D003561:Cytarabine; D016203:CDC2 Protein Kinase; D053143:Caspase 2; D053148:Caspase 3; D053453:Caspase 9