Synergistic killing effects of Stattic and arsenic trioxide on acute myeloid leukemia THP1 cell line and underlying mechanism

Changxue WU; Yan Zhao; Ting Zhang; Jian Zhang; Wenfeng YU; Hua Bai; Qifang Zhang

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Synergistic killing effects of Stattic and arsenic trioxide on acute myeloid leukemia THP1 cell line and underlying mechanism

VernacularTitle:Stattic增强三氧化二砷诱导急性髓样白血病THP1细胞生存和凋亡的机制
Author: Changxue WU ^{1
,

2} ; Yan ZHAO ^{1
,

2} ; Ting ZHANG ^{1
,

2} ; Jian ZHANG ^{1
,

2} ; Wenfeng YU ^{1
,

2} ; Hua BAI ³ ; Qifang ZHANG ^{1
,

2}
Author Information

1. Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, Guizhou Medical University, Guiyang 550004
2. Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang 550004
3. Central Laboratory, The Third Affiliated Hospital of Guizhou Medical University, Duyun 558000, China
Publication Type:Journal Article
Keywords: Stattic; arsenic trioxide; cell viability; apoptosis; acute myeloid leukemia; Nrf2
From: Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(1):53-58
CountryChina
Language:Chinese
Abstract: 【Objective】 To investigate the effects and mechanism of STAT3 inhibitor Stattic combined with arsenic trioxide (ATO) on the survival and apoptosis of acute myeloid leukemia (AML) THP1 cells. 【Methods】 CCK8 assay was used to detect the effects of Stattic combined with ATO on cell viability, flow cytometry was used to detect cellular apoptosis and ROS levels, and Caspase 3/7 Glo assay was used to determine Caspase 3/7 activity. qPCR was used to detect mRNA expression levels of GCLM, GCLC and HO-1 genes, and Western blotting was used to detect protein expression levels of P-STAT3, STAT3 and Nrf2. 【Results】 Stattic significantly inhibited the level of phosphorylated STAT3, aggravated the inhibitory effect of ATO on THP1 cell viability, and enhanced the apoptosis and reactive oxygen species (ROS) induced by ATO. Stattic significantly inhibited the expression of ATO-upregulated Nrf2 and the expression of Nrf2 downstream genes including HO-1, GCLM and GCLC. 【Conclusion】 Stattic can enhance the effects of ATO-mediated viability inhibition and apoptosis. The mechanism may be related to the increased ROS via inhibition of Nrf2 and Nrf2 downstream gene expression.