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

Autor: CAI Duo, LIANG Simin, ZHOU Qiao, WANG Li
Jazyk: čínština
Rok vydání: 2022
Předmět:
Zdroj: 陆军军医大学学报, Vol 44, Iss 13, Pp 1338-1348 (2022)
Druh dokumentu: article
ISSN: 2097-0927
88428591
DOI: 10.16016/j.2097-0927.202201220
Popis: 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, 1, 2 and 4 μmol/L), MMF alone groups (0.5, 1, 2, 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 (P < 0.01), and increased the apoptotic rate of K562 cells (P < 0.05). As compared with the MMF alone group, the combination group remarkably arrested the cell cycle at the G0/G1 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.
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