|Table of Contents|

mTORC2/mTORC1 inhibitor OSI-027 induces autophagic death of myelodysplastic syndrome/acute myeloid leukemia cells

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2022 04
Page:
583-588
Research Field:
Publishing date:

Info

Title:
mTORC2/mTORC1 inhibitor OSI-027 induces autophagic death of myelodysplastic syndrome/acute myeloid leukemia cells
Author(s):
YUE Qingfang1LIU Xinyue2ZHANG Yuan1CAO Fei1
1.Department of Oncology,Shaanxi Provincial People's Hospital,Shaanxi Xi'an 710068,China;2.Department of Hematology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Hubei Wuhan 430022,China.
Keywords:
myelodysplastic syndromeacute myeloid leukemiadual mTORC2/mTORC1 inhibitorautophagic death
PACS:
R733.71
DOI:
10.3969/j.issn.1672-4992.2022.04.005
Abstract:
Objective:To explore the effect of mTORC2/mTORC1 inhibitor OSI-027 on the proliferation of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) cell line SKM-1 and to further study the mechanisms regarding apoptosis and autophagy.Methods:We respectively tested the effects of different concentrations of mTORC1 inhibitor rapamycin and mTORC2/mTORC1 dual inhibitor OSI-027 on the proliferation,cycle and apoptosis of SKM-1 cells.Transmission electron microscopy was used to observe autophagic vacuoles and autophagosomes in the cells.Acridine orange staining method detected the number of acidic autophagic vacuoles.The mRNA expression and protein expression levels of autophagy-related genes Beclin-1 and LC3B were detected by RT-qPCR and Western-blot.Results:OSI-027 inhibited the proliferation of SKM-1 cells more significantly than rapamycin,and can block the cell cycle in G0/G1 phase,but OSI-027 could not effectively induce cell apoptosis.Transmission electron microscopy observed a large number of autophagic vacuoles and autophagosomes in the cytoplasm.Blocking autophagy cannot increase the proportion of cell apoptosis,but it can partially rescue the proliferation inhibition caused by OSI-027.After the intervention of OSI-027,autophagy-related genes Beclin-1 and LC3B were significantly up-regulated in mRNA and protein levels.Conclusion:The mTORC2/mTORC1 inhibitor OSI-027 can effectively cause autophagic death of SKM-1 cells and inhibit their proliferation.

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陕西省自然科学基础研究计划(编号:2019JM-563)
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