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Chidamide Inhibits Cell Proliferation via the PI3K/AKT Pathway in K562 Cells Based on Network Pharmacology and Experimental Validation

Abstract : 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 apoptosisvia 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.
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https://hal-cnrs.archives-ouvertes.fr/hal-03677226
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Submitted on : Tuesday, May 24, 2022 - 3:16:17 PM
Last modification on : Friday, August 5, 2022 - 12:01:43 PM

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Simin Liang, Xiaojia Zhou, Duo Cai, Fernando Rodrigues-Lima, Li Wang. Chidamide Inhibits Cell Proliferation via the PI3K/AKT Pathway in K562 Cells Based on Network Pharmacology and Experimental Validation. Current Pharmaceutical Design, 2021, 27 (26), pp.2990-2998. ⟨10.2174/1381612827666210701152250⟩. ⟨hal-03677226⟩

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