Objective       To determine of the ability of low dose triptolide (TPL) enhancing the cytotoxicity of idarubicin (IDA) in acute myeloid leukemia (AML) stem cells and its relationship with Nrf2 pathway

.        Methods       The CD34

+

CD38

-

KG1a cells were isolated from KG1a cells with flow cytometry and served as an AML stem cell model. The CD34

+

CD38

-

KG1a cells were subjected to different treatments (TPL

IDA

and TPL+IDA) and thereafter detected by MTT assay. Western blotting was used to determine the expression changes of Nrf2 after the treatments. RT-PCR was used to detect the mRNA levels of Nrf2 and its target genes including NQO1

GSR and HO-1.        Results       The proliferation of CD34

+

CD38

-

KG1a cells was inhibited by TPL and IDA separately with the 72 h IC

50

value of 20.48±1.60 nmol/L and 285.20±13.74 nmol/L

respectively. Low dose TPL (5 nmol/L) plus IDA showed higher cytotoxicity to CD34

+

CD38

-

KG1 cells than IDA alone

with 72h IC

50

value of 27.01±0.73 nmol/L (P0.01). Combination analysis showed synergistic effects of TPL and IDA. Western blot results displayed that Nrf2 expression was down-regulated in the cells treated with TPL combined with IDA. The mRNA expression of Nrf2 and downstream genes including NQO1

GSR

and HO-1 mRNA was decreased after TPL and IDA combined treatment (P0.01).        Conclusion       Low dose TPL may significantly enhance the cytotoxicity of IDA in AML stem cells through Nrf2 pathway.