Reversal Roles and Its Mechanism of Asiatic Acid on Multidrug Resistance in K562/ADR Cells Through the Wnt/β-catenin Pathway
10.19746/j.cnki.issn1009-2137.2024.06.010
- VernacularTitle:积雪草酸通过Wnt/β-catenin通路逆转白血病K562/ADR细胞的多药耐药性研究
- Author:
Ting ZHANG
1
;
Yong-Jiao LIU
;
Lei ZHANG
;
Xin-Yu ZHOU
;
Xiu-Hong JIA
Author Information
1. 滨州医学院附属医院儿科,山东滨州256603
- Keywords:
asiatic acid;
chronic myeloid leukemia;
multidrug resistance;
Wnt/β-catenin signaling pathway
- From:
Journal of Experimental Hematology
2024;32(6):1696-1703
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the reversal effect and mechanism of asiatic acid (AA)on multidrug resistance in human adriamycin (ADR)chronic myeloid leukemia K562/ADR cells.Methods:CCK-8 assay was used to detect the resistance of K562 cells and K562/ADR cells to ADR.CCK-8 assay was used to detect the effect of AA on K562/ADR cell viability and adriamycin sensitization.After K562/ADR cells were treated with non-toxic doses of AA(10,20μmol/L),the average fluorescence intensity of ADR was detected by flow cytometry.Real-time quantitative PCR was used to detect the expression levels of MRP1,P-gp,β-catenin,C-myc and cyclinD1 mRNA.Western blot was used to detect the expression levels of MRP1,P-gp,β-catenin,C-myc and cyclinD1 proteins.Western blot assay was used to detect the expression levels of MRP1,P-gp,β-catenin,C-myc and cyclinD1 proteins in K562/ADR cells treated with 20μmol/L AA and Wnt/β-catenin pathway agonist WAY-262611 (5 μmol/L).Results:The CCK-8 assay showed that the drug resistance of K562/ADR cells was 56.57 times that of K562 cells,showing stable drug resistance,and the difference was statistically significant (P<0.05 ).AA inhibited the proliferative activity of K562/ADR cells in a concentration-dependent manner(r=0.9666).Compared with 0 μmol/L AA group,the 10 and 20 μmol/L AA groups could significantly enhance the average fluorescence intensity of intracellular ADR (P<0.05 ),and reverse the cell resistance to ADR (P<0.05).The mRNA and protein expressions of MRP1,P-gp,β-catenin,C-myc and cyclinD1 in cells were down-regulated (P<0.05).Compared with 20μmol/L AA group,the expression levels of MRP1,P-gp,β-catenin,C-myc and cyclinD1 protein in 20 μmol/L AA+WAY group were significantly increased (P<0.05 ). Conclusion:AA inhibits K562/ADR cell proliferation in a concentration-dependent manner and reverse their resistance to ADR,the reversal mechanism may be related to the down-regulation of MRP1 and P-gp expression after inhibiting Wnt/β-catenin signaling pathway.
