Synergistic Effects of Glutamine Deprivation and Metformin in Acute Myeloid Leukemia
作者机构：Department of HematologyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China
出 版 物：《Current Medical Science》 (当代医学科学（英文）)
年 卷 期：2024年第44卷第4期
页 面：799-808页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：supported by the National Natural Science Foundation of China(No.82270177)
主 题：glutamine metformin acute myeloid leukemia metallothionein
摘 要：Objective The metabolic reprogramming of acute myeloid leukemia(AML)cells is a compensatory adaptation to meet energy requirements for rapid *** study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML *** SKM-1 cells(an AML cell line)were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide(BPTES,a glutaminase inhibitor)or *** viability was detected by Cell Counting Kit-8(CCK-8)assay,and cell apoptosis and reactive oxygen species(ROS)by flow *** blotting was conducted to examine the levels of apoptotic proteins,including cleaved caspase-3 and poly(ADP-ribose)polymerase(PARP).Moreover,the human long noncoding RNA(lncRNA)microarray was used to analyze gene expression after glutamine deprivation,and results were confirmed with quantitative RT-PCR(qRT-PCR).The expression of metallothionein 2A(MT2A)was suppressed using *** growth and apoptosis were further detected by CCK-8 assay and flow cytometry,respectively,in cells with MT2A *** Glutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 *** lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine ***2A knockdown increased apoptosis,while proliferation was not affected in SKM-1 *** addition,metformin inhibited cell growth and induced apoptosis in SKM-1 *** glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to ***,the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 *** Targeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML.
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