Chidamide, a selective histone deacetylase inhibitor, has antitumour effects. 5‑azacitidine (5‑AZA), a hypomethylating agent, is effective in treating acute myeloid leukaemia (AML) and myelodysplastic syndrome. However, to the best of our knowledge, the effect of chidamide and 5‑AZA on AML cell lines has not been fully investigated. In the present study, the antileukaemia activity of chidamide, alone and in combination with 5‑AZA, was assessed on different subtypes of AML cell lines (M1‑M5) and primary samples from several patients with AML in vitro. The results indicated that the proliferation of leukaemia cells was significantly and dose‑dependently inhibited by chidamide and 5‑AZA alone or in combination. The combination also had marked synergistic effects to induce apoptosis of AML cells. The apoptosis of leukaemia cells was induced via downregulation of BCL‑2 and myeloid‑cell leukemia 1 (MCL‑1) levels. Of note, chidamide also degraded the MCL‑1 protein in venetoclax‑resistant U937 cells, in which the MCL‑1 protein is upregulated. In addition, chidamide was able to induce myeloid differentiation (with CD11b upregulation) of AML cell lines or monocytic/dendritic differentiation (with CD86 upregulation) of primary cultured cells from several patients with AML. Chidamide was also able to promote the differentiation of the venetoclax‑resistant U937 cell line by upregulating CD11b expression. In conclusion, chidamide alone or combined with 5‑AZA may be an effective therapy for AML.
Keywords: 5‑azacitidine; acute myeloid leukaemia; apoptosis; chidamide; differentiation; proliferation.