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
,
2
;
Yu BAI
1
,
2
;
Dong-Ping WANG
1
,
2
;
Fu-Yan FAN
1
,
2
;
Yan-Qing SUN
1
,
3
Author Information
1. The First Clinical Medical College of Gansu University of Traditional Chinese Medicine
2. Lanzhou 730000, Gansu Province, China.
3. Lanzhou 730000, Gansu Province, China,Department of Hematology, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, China,E-mail: 18394496255@163.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.
