Chidamide plus decitabine synergistically induces apoptosis of acute myeloid leukemia cells by upregulating PERP.
Am J Transl Res
; 12(7): 3461-3475, 2020.
Article
em En
| MEDLINE
| ID: mdl-32774712
ABSTRACT
Acute myeloid leukemia (AML) is a malignant clonal disease that originates from hematopoietic stem cells. Because AML has a generally unsatisfactory long-term prognosis, new therapeutic options are required. To this end, we explored the effects of chidamide and decitabine alone or in combination on the AML cell lines THP-1, MV4-11, HL60, and Kasumi-1. Notably, the two drugs exhibited a synergistic effect against these cell lines. Similarly, we also found potential synergistic effects in primary cells of relapsed/refractory (r/r) AML. A transcriptome sequencing analysis performed to elucidate the underlying molecular mechanism revealed differentially expressed genes and regulatory pathways, particularly with regard to apoptosis, when comparing cells subjected to single and combination treatments. We identified PERP as a downstream target gene of the transcription factors P53 and P63, and it was expressed at considerably higher levels in combination-treated cells relative to monotherapy-treated cells. We further used a lentivirus-mediated small interfering RNA to inhibit the endogenous expression of PERP in AML cell lines and observed a significant increase in cell proliferation. Collectively, our results demonstrate, for the first time, the role of PERP in the response of AML to a combination drug regimen, providing a new potential treatment protocol and target in this context.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Guideline
/
Prognostic_studies
Idioma:
En
Revista:
Am J Transl Res
Ano de publicação:
2020
Tipo de documento:
Article