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  

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

作　　者：吴昌学[1,2] 赵艳[1,2] 张婷[1,2] 张健[1,2] 禹文峰[1,2] 柏华 张启芳[1,2] WU Changxue;ZHAO Yan;ZHANG Ting;ZHANG Jian;YU Wenfeng;BAI Hua;ZHANG Qifang(Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education,Guizhou Medical University, Guiyang 550004;Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang 550004;Central Laboratory,The Third Affiliated Hospital of Guizhou Medical University, Duyun 558000, China)

机构地区：[1]贵州医科大学地方病与少数民族性疾病教育部重点实验室,贵州贵阳550004 [2]贵州省医学分子生物学重点实验室,贵州医科大学,贵州贵阳550004 [3]贵州医科大学第三附属医院医学中心实验室,贵州都匀558000

出　　处：《西安交通大学学报（医学版）》2021年第1期53-58,共6页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.81560482,No.31960137);贵州省科技厅重点基金[黔科合基础(2016)1416];贵州省科技厅区域常见疾病与成体干细胞转化研究创新平台[黔科中引地(2019)4008号];贵州省科技厅支撑计划项目[黔科合支撑(2020)4Y129]。

摘　　要：目的探讨STAT3抑制剂Stattic联合三氧化二砷(arsenic trioxide,ATO)对急性髓系白血病(acute myeloid leukemia,AML)THP1细胞生存和凋亡的影响及其作用机制。方法以THP1细胞株为研究对象,用CCK8法检测Stattic联合ATO对THP1细胞生存的影响,用流式细胞术检测细胞凋亡、ROS水平,用Caspase 3/7 Glo assay试剂盒检测细胞Caspase 3/7活性,用qPCR检测mRNA表达,Western blotting检测蛋白表达。结果Stattic可明显抑制磷酸化STAT3的水平,显著加剧ATO对AML细胞生存抑制,增强ATO诱导的细胞凋亡和氧化应激产物。Stattic显著抑制ATO上调的Nrf2的表达以及下游基因的表达。结论Stattic可增强ATO对AML细胞生存抑制和凋亡诱导作用,其机制可能与抑制Nrf2和Nrf2下游基因表达引起ROS增多有关。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.

关 键 词：Stattic 三氧化二砷 THP1细胞 细胞生存 凋亡 NRF2 

分 类 号：R733.712[医药卫生—肿瘤]