Reversal Effect of Arctigenin on the Drug Resistance in Leukemia K562/A02 Cells and Its Mechanism
10.19746/j.cnki.issn1009-2137.2024.02.013
- VernacularTitle:牛蒡子苷元对白血病K562/A02细胞耐药性的逆转作用及机制
- Author:
Lin ZOU
1
;
Ye FANG
;
Wei HE
Author Information
1. 中国人民解放军中部战区总医院综合科,湖北武汉 430070
- Keywords:
arctigenin;
leukemia;
K562/A02 cells;
drug resistance;
TLR4/NF-κB signaling pathway
- From:
Journal of Experimental Hematology
2024;32(2):409-415
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the effect of arctigenin(ARG)on adriamycin(ADM)resistance of leukemia cell line K562/A02 and the underlying mechanism.Methods:Human leukemia cell line K562 and ADM-resistant cell line K562/A02 were cultured and treated with 2.5-50 μmol/L ADM.Cell proliferation was measured using CCK-8 method,and half maximal inhibitory concentration(IC50)was calculated.K562/A02 cells were treated with different concentrations of ARG(1,2,4,8,16 mmol/L)to detect the effect of ARG on K562/A02 cells,and a suitable concentration(2 mmol/L)was selected for subsequent experiments.K562/A02 cells were treated with 2 mmol/L ARG and 5 μmol/L ADM,and cell apoptosis was detected by flow cytometry,the expression of P-gp,MRP,cleaved caspase-3,Bax,Bcl-2 proteins and the TLR4/NF-κB signaling pathway-related proteins were measured by Western blot.TLR4 overexpression plasmid was transfected into K562/A02 cells which were co-treated with ARG and ADM.then drug sensitivity and cell apoptosis were measured.Results:The IC50 value of ADM on K562/A02 cells was 36.57 μmol/L,which was significantly higher than that on K562 cells(1.30 μmol/L).ARG with a concentration of≤2 mmol/L did not have a significant effect on K562/A02 cells.2 mmol/L ARG significantly reduced the IC50 of ADM on K562/A02 cells.In 5 μmol/L ADM-treated K562/A02 cells,compared with the control group,the apoptosis rate of K562/A02 cells in the ARG group was significantly increased,the expressions of cleaved caspase-3,Bax proteins were significantly upregulated,the expressions of P-gp,MRP,Bcl-2,TLR4.MyD88,and p-NF-k B proteins were significantly downregulated,and the differences were statistically significant(P＜0.05).After transfection with TLR4 overexpression plasmid,the sensitivity of ARG-treated K562/A02 cells to ADM was reduced(P＜0.05),the cell apoptosis was decreased,and the expressions of P-gp,MRP,Bcl-2 and TLR4/NF-κB signaling pathway-related proteins were significantly elevated,while the expressions of cleaved caspase-3 and Bax proteins were significantly decreased(all P＜0.05).Conclusion:ARG may reverse the resistance of human leukemia cell line K562/A02 to ADM by inhibiting TLR4/NF-κB signaling pathway.
