Mechanistic Study of ATO and MET Synergistically Promoting Apoptosis in Leukemia Cells
10.19746/j.cnki.issn1009-2137.2025.06.009
- VernacularTitle:ATO联合MET协同促进白血病细胞凋亡的机制研究
- Author:
Meng LIU
1
;
Li-Wen-Hui HUANG
;
Xiao-Hui SI
;
Xin-Qing NIU
Author Information
1. 新乡医学院医学技术学院,河南省免疫与靶向药物重点实验室,河南省分子诊断与医学检验技术协同创新中心,河南新乡 453003
- Publication Type:Journal Article
- Keywords:
leukemia;
arsenic trioxide;
metformin;
autophagy;
PI3K/Akt;
AMPK
- From:
Journal of Experimental Hematology
2025;33(6):1609-1616
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the mechanism of arsenic trioxide(ATO)combined with metformin(MET)in promoting apoptosis of leukemia cells.Methods:CCK-8 method was used to detect the viability of leukemia cell line KG1a,K562,and THP1 cells treated by ATO monotherapy,MET monotherapy,and ATO combined with MET.Flow cytometry was used to detect cell cycle and apoptosis.RT-qPCR was used to detect the mRNA expression of PI3K/Akt and LKB1/AMPK pathway-related genes.Western blot was used to detect the expression of PI3K/Akt and LKB1/AMPK pathway-related proteins and autophagy-related protein LC3B and P62.Results:Compared with the ATO monotherapy group,ATO combined with MET significantly inhibited the growth of KG1a,K562 and THP1 cells,and the difference in KG1a cells was more statistically significant.The combination of the two drugs induced KG1a cell cycle arrest,promoted apoptosis,increased the expression of autophagy-related protein LC3B and P62,up-regulated the mRNA expression levels of PI3K/Akt pathway and LKB1/AMPK pathway-related genes,as well as the expression of LKB1/AMPK pathway-related proteins,and down-regulated the expression of PI3K/Akt pathway-related proteins.Conclusion:ATO combined with MET promotes apoptosis by up-regulating LKB1/AMPK and down-regulating PI3K/Akt signaling pathway to regulate the autophagy of leukemia cells.
