Chidamide combined with mycophenolate mofetil suppress proliferation of secondary acute myeloid leukemia cells

Duo CAI; Simin LIANG; Qiao ZHOU; Li WANG

doi:10.16016/j.2097-0927.202201220

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Chidamide combined with mycophenolate mofetil suppress proliferation of secondary acute myeloid leukemia cells

Basic Medicine | 更新时间：2026-01-09

- Chidamide combined with mycophenolate mofetil suppress proliferation of secondary acute myeloid leukemia cells
- Journal of Army Medical University Vol. 44, Issue 13, Pages: 1338-1348(2022)
- 作者机构：
  
  1.400016 重庆，重庆医科大学附属第一医院：血液内科
  2.400016 重庆，重庆医科大学附属第一医院：重大代谢性疾病转化医学重点实验室
- 作者简介：
- 基金信息：
  
  the Key Project of Joint Medical Scientific Research of Chongqing Science and Technology Commission and Chongqing Health Commission(2018ZDXM001)
- DOI：10.16016/j.2097-0927.202201220
  CLC： R733.7;R965;R979.1
- Received：23 January 2022，
  
  Revised：2022-03-05，
  
  Published：15 July 2022
- 稿件说明：
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Duo CAI, Simin LIANG, Qiao ZHOU, et al. Chidamide combined with mycophenolate mofetil suppress proliferation of secondary acute myeloid leukemia cells[J]. Journal of Army Medical University, 2022, 44(13): 1338-1348.
DOI：

Duo CAI, Simin LIANG, Qiao ZHOU, et al. Chidamide combined with mycophenolate mofetil suppress proliferation of secondary acute myeloid leukemia cells[J]. Journal of Army Medical University, 2022, 44(13): 1338-1348. DOI： 10.16016/j.2097-0927.202201220.

摘要

目的

探讨西达本胺(chidamide，CDM)和吗替麦考酚酯(mycophenolate mofetil，MMF)联合应用对继发性急性髓系白血病细胞增殖的影响。

方法

慢性髓系白血病急变期细胞株K562及MDS转白细胞株SKM-1，分别按照不同浓度的CDM单药组(0.25、0.5、1、2、4 μmol/L)，MMF单药组(0.5、1、2、4、8 μmol/L)及联合用药组(CDM∶MMF=1∶2)干预24、48、72 h后，CCK-8实验检测细胞增殖抑制率。基于最佳联合干预浓度干预72 h后，流式细胞学检测细胞周期及凋亡率的变化，并通过网络药理学探讨其作用机制。

结果

CCK-8结果显示，联合组(1 μmol/L CDM+2 μmol/L MMF)在K562和SKM-1细胞中的联合指数分别为0.389 44和0.630 98。与CDM及MMF单药组比较，联合用药能显著提高对K562和SKM-1细胞增殖抑制率(

0.01)，并促进K562细胞凋亡率增高(

0.05)。相较单药MMF组，联合组显著诱导K562、SKM-1细胞G

期阻滞，但较CDM单药无统计学差异。其后网络药理学构建出66个节点、222条边的药物-疾病靶点PPI网络，并根据拓扑学筛选出CDK1、CDK2、CDK4、CDK6、CDK9、SYK、BTK、KDR、PIK3CB等9个核心靶点，富集分析主要涉及蛋白质磷酸化、细胞增殖、凋亡调控等多种生物进程，及PI3K-AKT、FOXO等信号通路。

结论

CDM联合MMF可显著抑制继发性急性髓系白血病细胞生长。

Abstract

Objective

To investigate the effects of combined application of chidamide (CDM) and mycophenolate mofetil (MMF) on the proliferation of secondary acute myeloid leukemia (sAML) cells.

Methods

Chronic myeloid leukemia blast-phase cell line K562 and myelodysplastic syndromes (MDS)-transformed leukocyte line SKM-1 were employed in the study. The cells were divided into groups according to different concentrations of intervention drugs: CDM alone groups (0.25

0.5

2 and 4 μmol/L)

MMF alone groups (0.5

4 and 8 μmol/L) and combined drug groups (CDM∶MMF=1∶2)

respectively. The inhibitory rate of cell proliferation was detected by CCK-8 assay after treatment for 24

48 and 72 h

respectively. Moreover

the changes of cell cycle and apoptotic rate were determined by flow cytometry after 72 h of intervention under the optimal combined drug concentration

and its mechanism was analyzed by network pharmacology.

Results

CCK-8 assay showed that the combination index of the combined drug group (1 μmol/L CDM+2 μmol/L MMF) was 0.389 44 in K562 cells and 0.630 98 in SKM-1 cells. When compared with the CDM and MMF monotherapy groups

the combined treatment significantly enhanced the inhibitory effect on the proliferation of both K562 and SKM-1 cells (

0.01)

and increased the apoptotic rate of K562 cells (

0.05). As compared with the MMF alone group

the combination group remarkably arrested the cell cycle at the G

phase

though which had no statistical difference with CDM alone. Subsequently

a drug-disease target protein-protein interaction (PPI) network including 66 nodes and 222 edges was constructed through network pharmacology

and 9 core targets including CDK1

CDK2

CDK4

CDK6

CDK9

SYK

BTK

KDR

and PIK3CB were screened out according to topology. Enrichment analysis indicated that various biological processes such as protein phosphorylation

cell proliferation

and apoptosis regulation were mainly involved

as well as PI3K-AKT

FOXO and other signaling pathways.

Conclusion

CDM combined with MMF significantly inhibits the growth of sAML cells.

关键词

Keywords

references

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