Background: Chidamide, a novel benzamide-type histone deacetylase (HDAC) inhibitor, exerts antitumor
effects on several types of cancer. However, the role of Chidamide in chronic myeloid leukemia (CML)
remains elusive. Therefore, the present study aimed to investigate the effects of Chidamide on CML cell proliferation
and explore its underlying mechanism.
Methods: Cell proliferation was assessed by CCK-8 assay, cell cycle distribution and apoptosis were detected
by flow cytometry and the expression of related proteins was evaluated by western blot analysis. The potential
mechanisms were systematically explored by the network-based pharmacological methods, including Gene Ontology
and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses.
Results: The results revealed that Chidamide inhibited the proliferation of K562 cells in a dose- and time-dependent
manner. In addition, Chidamide blocked cells in the G0/G1 phase via downregulating cyclin-dependent kinase
4, and induced apoptosis via upregulating Bax and downregulating of Bcl-2. Additionally, using network-
based pharmacological methods, we found that PI3K/AKT signaling pathway is involved and significantly
related to cell proliferation in CML. Intriguingly, cell treatment with Chidamide suppressed the activation of
the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway via decreasing the levels of
phosphorylated (p)-PI3K and p-AKT. Moreover, insulin-like growth factor 1 (IGF-1), a PI3K/AKT activator, reversed
the inhibitory effects of Chidamide on K562 cell proliferation.
Conclusion: The study demonstrated that Chidamide may inhibit the proliferation of K562 cells by promoting
cell cycle arrest and apoptosis via suppressing the PI3K/AKT pathway, suggesting that Chidamide could be a
promising approach to the treatment of CML.