Inhibition of autophagy overcomes glucocorticoid resistance in lymphoid malignant cells

Cancer Biology & Therapy
Lei JiangQuentin Liu

Abstract

Glucocorticoid (GC) resistance remains a major obstacle to successful treatment of lymphoid malignancies. Till now, the precise mechanism of GC resistance remains unclear. In the present study, dexamethasone (Dex) inhibited cell proliferation, arrested cell cycle in G0/G1-phase, and induced apoptosis in Dex-sensitive acute lymphoblastic leukemia cells. However, Dex failed to cause cell death in Dex-resistant lymphoid malignant cells. Intriguingly, we found that autophagy was induced by Dex in resistant cells, as indicated by autophagosomes formation, LC3-I to LC3-II conversion, p62 degradation, and formation of acidic autophagic vacuoles. Moreover, the results showed that Dex reduced the activity of mTOR pathway, as determined by decreased phosphorylation levels of mTOR, Akt, P70S6K and 4E-BP1 in resistant cells. Inhibition of autophagy by either chloroquine (CQ) or 3-methyladenine (3-MA) overcame Dex-resistance in lymphoid malignant cells by increasing apoptotic cell death in vitro. Consistently, inhibition of autophagy by stably knockdown of Beclin1 sensitized Dex-resistant lymphoid malignant cells to induction of apoptosis in vivo. Thus, inhibition of autophagy has the potential to improve lymphoid malignancy treatment by ov...Continue Reading

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Citations

May 2, 2016·Blood Reviews·Zhiwu DongKewen Zhao
Jun 5, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Cui YangQuan Xia
Dec 14, 2016·Blood·Patrick Auberger, Alexandre Puissant
Jun 27, 2018·Current Drug Targets·Tiantian WangChengqi He
Sep 10, 2019·Journal of Cellular and Molecular Medicine·Dongyi PengYuxin Tang
Oct 16, 2018·Frontiers in Cell and Developmental Biology·Angela IannicielloG Vignir Helgason
Nov 1, 2017·World Journal of Gastroenterology : WJG·Karen Dubois-CamachoMarcela A Hermoso
Oct 12, 2018·Medicinal Research Reviews·Hendrik FolkertsValerie R Wiersma
Mar 12, 2020·Apoptosis : an International Journal on Programmed Cell Death·Tiantian WangChengqi He
Jan 12, 2021·Frontiers in Pharmacology·Marta VomeroCristiano Alessandri
Sep 21, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Dorien ClarisseKarolien De Bosscher

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Methods Mentioned

BETA
Flow cytometry
transmission electron microscopy
confocal microscopy

Software Mentioned

CELL Quest

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