广东医学2017,Vol.38Issue(6):817-820,4.
低浓度雷公藤内酯联合伊达比星在急性髓系白血病干细胞凋亡中的作用
Low-dose triptolide in combination with idarubicin induces apoptosis in acute myeloid leukemia stem cells
摘要
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.关键词
急性髓系白血病干细胞/雷公藤内酯/伊达比星/MDR1基因Key words
acute myeloid leukemia stem cells/Tripelide/IDA/MDR1 gene引用本文复制引用
唐家宏,徐兵,李妍妍,陈菲莉,陈凯,周淑芸..低浓度雷公藤内酯联合伊达比星在急性髓系白血病干细胞凋亡中的作用[J].广东医学,2017,38(6):817-820,4.基金项目
国家自然科学基金资助项目(编号:81570156) (编号:81570156)