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丁酸钠和帕比司他通过多种途径诱导慢性髓性白血病细胞凋亡。

Sodium butyrate and panobinostat induce apoptosis of chronic myeloid leukemia cells via multiple pathways.

作者信息

Jia Xiaoyuan, Zheng Yinsuo, Guo Yanzi, Chen Kan

机构信息

College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.

Department of Hematology, Baoji Central Hospital, Baoji, China.

出版信息

Mol Genet Genomic Med. 2019 May;7(5):e613. doi: 10.1002/mgg3.613. Epub 2019 Mar 19.

DOI:10.1002/mgg3.613
PMID:30891950
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6503025/
Abstract

PURPOSE

Histone deacetylase inhibitor (HDACI) is a novel therapeutic option for cancer. However, the effects of HDACIs on chronic myeloid leukemia (CML) and the underlying mechanisms are still unknown. The aim of this study was to investigate the effect and the mechanism-of-action of two HDACI members, sodium butyrate (NaBu) and panobinostat (LBH589) in K562 and the adriamycin-resistant cell line K562/ADR.

METHODS

Cell viability was assessed using MTT assay. Cell apoptosis was detected with flow cytometry. Cell cycle analysis and western blot were performed to explore the possible molecules related to HDACIs effects.

RESULTS

The effect of NaBu was more powerful on K562/ADR than on K562 cells. LBH589 triggered apoptosis and inhibited the growth of K562 cells. Both HDACIs inhibited K562 and K562/ADR cells via activation of intrinsic/extrinsic apoptotic pathways and inhibition of AKT-mTOR pathway while NaBu also activated endoplasmic reticulum stress (ERS) mediated apoptotic pathway in K562/ADR cells. LBH589 reduced the expression of drug-resistant related proteins in K562 cells. However, neither NaBu nor LBH589 could significantly influence the expression of the drug-resistant related proteins in K562/ADR cells.

CONCLUSION

The combination of HDACI and other therapeutic strategies are likely required to overcome drug resistance in CML therapy.

摘要

目的

组蛋白去乙酰化酶抑制剂（HDACI）是一种新型癌症治疗选择。然而，HDACIs对慢性粒细胞白血病（CML）的影响及其潜在机制仍不清楚。本研究旨在探讨两种HDACI成员丁酸钠（NaBu）和帕比司他（LBH589）对K562细胞及阿霉素耐药细胞系K562/ADR的作用及作用机制。

方法

采用MTT法评估细胞活力。用流式细胞术检测细胞凋亡。进行细胞周期分析和蛋白质印迹法以探索与HDACIs作用相关的可能分子。

结果

NaBu对K562/ADR细胞的作用比对K562细胞更强。LBH589诱导K562细胞凋亡并抑制其生长。两种HDACIs均通过激活内源性/外源性凋亡途径和抑制AKT-mTOR途径来抑制K562和K562/ADR细胞，而NaBu还激活K562/ADR细胞中内质网应激（ERS）介导的凋亡途径。LBH589降低K562细胞中耐药相关蛋白的表达。然而，NaBu和LBH589均不能显著影响K562/ADR细胞中耐药相关蛋白的表达。

结论

在CML治疗中，可能需要将HDACI与其他治疗策略联合使用以克服耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f5/6503025/46a9eab0a7c2/MGG3-7-e613-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f5/6503025/49c2d9d79be0/MGG3-7-e613-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f5/6503025/4bf1193a9ad0/MGG3-7-e613-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f5/6503025/b54855cbed0b/MGG3-7-e613-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f5/6503025/a8994160f09c/MGG3-7-e613-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f5/6503025/dead227b84c8/MGG3-7-e613-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f5/6503025/46a9eab0a7c2/MGG3-7-e613-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f5/6503025/49c2d9d79be0/MGG3-7-e613-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f5/6503025/4bf1193a9ad0/MGG3-7-e613-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f5/6503025/b54855cbed0b/MGG3-7-e613-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f5/6503025/a8994160f09c/MGG3-7-e613-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f5/6503025/dead227b84c8/MGG3-7-e613-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f5/6503025/46a9eab0a7c2/MGG3-7-e613-g006.jpg

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