[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].

Autor: Feng WW; The First Clinical Medical College of Gansu University of Traditional Chinese Medicine; Lanzhou 730000, Gansu Province, China., Bai Y; The First Clinical Medical College of Gansu University of Traditional Chinese Medicine; Lanzhou 730000, Gansu Province, China., Wang DP; The First Clinical Medical College of Gansu University of Traditional Chinese Medicine; Lanzhou 730000, Gansu Province, China., Fan FY; The First Clinical Medical College of Gansu University of Traditional Chinese Medicine; Lanzhou 730000, Gansu Province, China., Sun YQ; 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@163.com.
Jazyk: čínština
Zdroj: Zhongguo shi yan xue ye xue za zhi [Zhongguo Shi Yan Xue Ye Xue Za Zhi] 2023 Jun; Vol. 31 (3), pp. 621-627.
DOI: 10.19746/j.cnki.issn.1009-2137.2023.03.001
Abstrakt: 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 G 0 /G 1 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.
Databáze: MEDLINE
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