Abstract: 【Objective】 To investigate the effect of low-dose triptolide (TRI) in combination with idarubicin (IDA) on acute myeloid leukemia stem cells and the relationship with HIF-1α pathway. 【Methods】 CD34+CD38-KG1a cells was sorted from KG1a cell lines by fluorence-activated cell sorting (FACS) analysis. Immunophenotype and cell cycle analysis of CD34+CD38-KG1a cells were analyzed by fluorescence-activated cell sorting analysis. Annexin-V/PI double staining was used to detect the effects of low-dose TRI in combination with IDA on apoptosis of CD34+CD38-KG1a cells. Western bloting to analyze the expression of HIF-1α and its downstream protein CXCR4

VLA-4 in CD34+CD38-KG1a cells after treatment with TRI

IDA

and TRI+IDA. 【Results】 After sorting

98.15 ± 1.64% of the cells were labeled for CD34+CD38-. Cell cycle analysis also showed that proportion of G0/G1 cells was 82.4 ± 3.82%. CD34+CD38-KG1a cells were exposed to 5 nmol/L TPL

27 nmol/L IDA and TRI+IDA for 24 h. The apoptotic cells were determined by PI/Annexin V staining and flow cytometric analysis. Apoptotic ratio of cells treated by IDA with TPL was significantly increased compared to cells treated by IDA alone (24.85 ± 1.70% vs. 76.87 ± 8.34%

P < 0.001). Western blot results showed markedly decrease the expression of HIF-1α

CXCR4 and VLA-4 in CD34+CD38-KG1a cells treated with low-dose TRI in combination with IDA. 【Conclusion】 A relatively low concentration of TPL in combination with IDA could induce apoptosis of AML stem cells in vitro via inhibition of HIF-1α pathway.