Inhibition of autophagy enhances apoptosis induced by bortezomib in AML cells.
NB4 cells
acute promyelocytic leukaemia
apoptosis
autophagy
bortezomib
Journal
Oncology letters
ISSN: 1792-1074
Titre abrégé: Oncol Lett
Pays: Greece
ID NLM: 101531236
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
08
03
2020
accepted:
12
11
2020
entrez:
30
12
2020
pubmed:
31
12
2020
medline:
31
12
2020
Statut:
ppublish
Résumé
Bortezomib is a novel proteasome inhibitor, which has been successfully used to treat mantle cell lymphoma and multiple myeloma. However, the direct effects of bortezomib on acute promyelocytic leukaemia (APL) have not been fully investigated. In the present study, the WST-8 assay, western blotting, flow cytometry, monodansylcadaverine staining and transmission electron microscopy were performed. It was demonstrated that bortezomib treatment induced a time- and dose-dependent decrease in the viability of NB4 cells. Bortezomib treatment induced cell apoptosis in NB4 cells, as assessed by Annexin V/propidium iodide analysis, and the detection of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, Bax and Bcl-2 expression. Furthermore, bortezomib treatment induced autophagy in NB4 cells, as indicated by autophagosome formation, p62 degradation, LC3-I to LC3-II conversion and formation of acidic autophagic vacuoles. Notably, autophagy induced by bortezomib was initiated prior to apoptosis. Inhibition of autophagy by knocking down Beclin-1 expression increased bortezomib-induced apoptosis in NB4 cells. Therefore, the present study revealed that the combination of bortezomib and autophagy inhibition may be a potential treatment strategy for APL.
Identifiants
pubmed: 33376542
doi: 10.3892/ol.2020.12370
pii: OL-0-0-12370
pmc: PMC7751351
doi:
Types de publication
Journal Article
Langues
eng
Pagination
109Informations de copyright
Copyright: © Jiang et al.
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