STAT3 signaling pathway is involved in decitabine induced biological phenotype regulation of acute myeloid leukemia cells.

ABSTRACT

OBJECTIVE: This study aimed to investigate the role of signal transduction and transcriptional activator STAT3 and relevant signaling pathway in the DAC regulated biological phenotype of AML cells. METHODS: The effect of DAC at different concentrations on the proliferation of HL-60 cells was determined. After DAC treatment for 48 h, the killing capability of NK cells against HL-60 cells and the protein expressions of STAT3, JAK1, JAK2, SOCS-1 and SOCS-3 were evaluated. RESULTS: DAC markedly inhibited the proliferation of HL-60 cells. After the treatment of 48 hr with 0.2, 0.5 and 1.0 mol/L DAC, the HL-60 viability was reduced by 25±13%, 39±8% and 50±7% (P<0.01), respectively, and the early apoptosis rate was increased to 24.77±7.5%, 27.1±4.48% and 30.53±3.93%, respectively (control 3.11±0.12%, P<0.01). DAC up-regulated the expression of MICA/B, ULBP-1 and ULBP-3 in HL-60 cells, and increased the killing activity of NK cells to HL-60 cells. DAC significantly induced the apoptosis of HL-60 cells and up-regulated the expression of NKG2D ligands in a dose dependent manner. Western blot assay showed the protein expression of STAT3, JAK, JAK2, phosphorylated STAT3, phosphorylated JAK1 and phosphorylated JAK2 decreased, while that of SOCS-1 and SOCS-3 increased in HL-60 cells after DAC treatment. CONCLUSION: In HL-60 cells, DAC can markedly inhibit their proliferation and up-regulate the expression of NKG2D ligands, and DAC also increase the cytotoxicity of NK cells to HL-60 cells, which may be related to the STAT3 related signaling pathway.