Effects of chidamide and its combination with decitabine on proliferation and apoptosis of leukemia cell lines

摘要

Chidamide, a novel histone deacetylase inhibitor (HDACI), shows anticancer ability against leukemia and solid tumors. Decitabine (5-Aza-2’-deoxycytidine, DAC), an anti-leukemic drug, is effective in treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In our study, we investigated the anti-leukemic ability of chidamide, as well as its combination with decitabine in leukemia cells (HL60 and NB4). The results showed that the inhibitive effect of chidamide was dose- and time-dependent at concentration of 0.25-8 μM. The proliferation of HL60 and NB4 cells were significantly inhibited by chidamide or its combination with decitabine. The combination had a remarkable synergistic anti-leukemic effect. Chidamide increased the levels of acetylated histone H3 in both HL60 and NB4 cells by effectively inhibiting histone deacetylases (HDAC) enzymatic activities. The cells were blocked in G0/G1 phase by chidamide, but when chidamide was combined with decitabine, the cell cycle was mainly blocked in G2/M phase, accompanied by the induction of p21 expression. In both cases (chidamide or chidamide combined with decitabine), apoptosis of tumor cells was induced through up-regulation of Bax and Caspase-3, and down-regulation of Bcl-2, showing a synergistic cytotoxicity. In conclusion, our results suggested that chidamide in combination with decitabine might be an effective therapy for AML.