Inhibition of autophagy enhances apoptosis induced by bortezomib in AML cells

Jiang,Lei; Zhao,Yi-Ming; Yang,Ming-Zhen

doi:10.3892/ol.2020.12370

Inhibition of autophagy enhances apoptosis induced by bortezomib in AML cells

Authors:
- Lei Jiang
- Yi-Ming Zhao
- Ming-Zhen Yang
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Affiliations: Department of Haematology, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230012, P.R. China
Published online on: December 11, 2020 https://doi.org/10.3892/ol.2020.12370
Article Number: 109
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 the NB4 cells. Therefore, the present study revealed that the combination of bortezomib and autophagy inhibition may be a potential treatment strategy for APL.

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