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.
MeSH terms
-
Animals
-
Antimetabolites, Antineoplastic / pharmacology
-
Apoptosis Regulatory Proteins / biosynthesis
-
Apoptosis*
-
Autophagy*
-
Autophagy-Related Protein 5
-
Beclin-1
-
Bone Morphogenetic Protein 4 / genetics
-
Bone Morphogenetic Protein 4 / metabolism*
-
CDC2 Protein Kinase / biosynthesis
-
Caspase 2 / metabolism
-
Caspase 3 / metabolism
-
Caspase 9 / metabolism
-
Cell Line, Tumor
-
Cell Proliferation
-
Cyclin B1 / biosynthesis
-
Cytarabine / pharmacology
-
Drug Resistance, Neoplasm*
-
Enzyme Activation
-
Female
-
Humans
-
Leukemia, Myeloid / drug therapy*
-
Leukemia, Myeloid / physiopathology*
-
Membrane Proteins / biosynthesis
-
Mice
-
Mice, Nude
-
Microtubule-Associated Proteins / biosynthesis
-
Neoplasm Transplantation
-
RNA Interference
-
RNA, Small Interfering
-
Up-Regulation
-
Xenograft Model Antitumor Assays
Substances
-
ATG5 protein, human
-
Antimetabolites, Antineoplastic
-
Apoptosis Regulatory Proteins
-
Autophagy-Related Protein 5
-
BECN1 protein, human
-
BMP4 protein, human
-
Beclin-1
-
Bone Morphogenetic Protein 4
-
CCNB1 protein, human
-
Cyclin B1
-
MAP1LC3A protein, human
-
Membrane Proteins
-
Microtubule-Associated Proteins
-
RNA, Small Interfering
-
Cytarabine
-
CDC2 Protein Kinase
-
Caspase 2
-
Caspase 3
-
Caspase 9