Study on the Mechanism of Multi-Drug Resistance of Agaricus Blazei Extract FA-2-b-β Mediated Wnt Signaling Pathway to Reverse Acute T Lymphoblastic Leukemia.
10.19746/j.cnki.issn.1009-2137.2023.03.001
- Author:
Wen-Wen FENG
1
;
Yu BAI
1
;
Dong-Ping WANG
1
;
Fu-Yan FAN
1
;
Yan-Qing SUN
2
,
3
Author Information
1. The First Clinical Medical College of Gansu University of Traditional Chinese Medicine; Lanzhou 730000, Gansu Province, China.
2. The First Clinical Medical College of Gansu University of Traditional Chinese Medicine; Lanzhou 730000, Gansu Province, China,Department of Hematology, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, China,E-mail: 18394496255@
3. com.
- Publication Type:Journal Article
- Keywords:
Agaricus blazei;
Wnt signaling pathway;
acute T lymphoblastic leukemia;
multi-drug resistance
- MeSH:
Humans;
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma;
Wnt Signaling Pathway;
Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism*;
Apoptosis;
Drug Resistance, Multiple;
Membrane Proteins;
Cell Line, Tumor;
Cell Proliferation
- From:
Journal of Experimental Hematology
2023;31(3):621-627
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the mechanism of drug reversing resistance of Agaricus blazei extract FA-2-b-β on T cell acute lymphoblastic leukemia (T-ALL) cell lines.
METHODS:Cell proliferation was detected by CCK-8 assay; the apoptosis, cell cycle mitochondrial membrane potential, and intracellular rhodamine accumulation were detected by flow cytometry, and apoptosis-related gene and protein expression were detected by qPCR and Western blot; the membrane surface protein MDR1 was observed by immunofluorescence microscopy.
RESULTS:Different concentrations of FA-2-b-β significantly inhibited proliferation and induced apoptosis of CCRF-CEM and CEM/C1 (P<0.05), and CCRF-CEM cell cycle were arrested at S phase, and CEM/C1 cells were arrested at G0/G1 phase. Western blot and qPCR results show that FA-2-b-β inhibited ABCB1、ABCG2、CTNNB、MYC and BCL-2 expression, but upregulated Bax expression. In addition, FA-2-b-β reversed the resistance characteristics of CEM/C1 drug-resistance cells, which decreased mitochondrial membrane potential, and significantly increased the intracellular rhodamine accumulation, and weakening of the expression of the membrane surface protein MDR1. With the Wnt/β-catenin inhibitor (ICG001), the process was further intensified.
CONCLUSION:Agaricus Blazei Extract FA-2-b-β inhibits cell proliferation, promotes apoptosis, regulates the cell cycle, reduces mitochondrial energy supply, and down-regulate MDR1 expression to reverse the resistance of CEM/C1, which all suggest it is through regulating the Wnt signaling pathway in T-ALL.
