Low-dose triptolide in combination with idarubicin induces apoptosis in acute myeloid leukemia stem cells
TANG Jia-hong
XU Bing
LI Yan-yan
CHEN Fei-li
CHEN Kai
ZHOU Shu-yun
Abstract：Objective To investigate the role of MDR1 in the cytotoxicity of low-dose tripelide (TPL) in combination with Idarubicin (IDA) on acute myeloid leukemia (AML) stem cells.Methods CD34 + CD38-KG1a cells sorted from KG1a cell line by MACS were subjected to TPL alone,IDA alone and their combination for 24 hours.The apoptotic rate of CD34 + CD38-KG1a cells was determined by flow cytometry with Annexin V/PI double staining.The mRNA expression of MDR1 was measured by SYBR RT-PCR.Western blot analysis was performed to detect the protein expression of MDRI.Results After exposure to 5 nmol/L TPL (IC20) alone,27 nmol/L IDA (IC50) alone,and 5 nmol/L TPL with 27 nmol/L IDA,the apoptotic rates of CD34 + CD38-KG1 a cells were (18.07 ± 0.32) ％,(20.13 ± 0.06) ％,and (60.17 ± 1.45)％,respectively.The combination of TPL and IDA-inducing apoptosis was significantly increased compared to IDA or TPL alone.According to RT-PCR results,the mRNA expression of MDR1 could be reduced by TPL alone,IDA alone and their combination.Compared to the control group (0.927 ± 0.084),the relative expression of MDR1 was 0.462 ±0.048,0.396 ± 0.019,and 0.231 ± 0.023,respectively.A remarkable suppression of MDR1 was observed in the combination group.Western blot results further confirmed a marked inhibition of MDRI in the combination group.Conclusion Low-dose TPL significantly enhanced the cytotoxicity of IDA in AML stem cells via inhibition of MDR1 expression.
Keywords：acute myeloid leukemia stem cellsTripelideIDAMDR1 gene
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 817-820 )