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 / 中国实验血液学杂志
Journal of Experimental Hematology
; (6): 621-627, 2023.
Article
em Zh
| WPRIM
| ID: wpr-982107
Biblioteca responsável:
WPRO
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.
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Índice:
WPRIM
Assunto principal:
Apoptose
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Resistência a Múltiplos Medicamentos
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Linhagem Celular Tumoral
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Proliferação de Células
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Leucemia-Linfoma Linfoblástico de Células T Precursoras
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Via de Sinalização Wnt
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Proteínas de Membrana
Limite:
Humans
Idioma:
Zh
Revista:
Journal of Experimental Hematology
Ano de publicação:
2023
Tipo de documento:
Article