Dobutamine Enhances the Targeted Inhibitory Effect of Quizar-tinib on FLT3-ITD Mutant Acute Myeloid Leukemia
10.19746/j.cnki.issn1009-2137.2024.04.015
- VernacularTitle:多巴酚丁胺可增强奎扎替尼对FLT3-ITD突变型急性髓系白血病的靶向抑制作用
- Author:
Yu-Ang GAO
1
,
2
;
Qian-Yu ZHANG
;
Xin LI
;
Shen-Yu WANG
;
Ji-Hui LI
;
Yang XUE
;
Chang-Yan LI
;
Hong-Mei NING
Author Information
1. 解放军医学院研究生院
2. 中国人民解放军总医院第五医学中心血液病医学部,北京 100071
- Keywords:
acute myeloid leukemia;
fms-like tyrosine kinase 3;
dobutamine;
YAP1
- From:
Journal of Experimental Hematology
2024;32(4):1071-1077
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the inhibitory effect of dobutamine on proliferation of FLT3-ITD mutated acute myeloid leukemia(AML)cells and explore the feasibility of dobutamine as a monotherapy or in combination with quizartinib for the treatment of this type of AML.Methods:FLT3-ITD mutant cell lines MOLM13 and MV4-11 were cultured in vitro and divided into control group,dobutamine treatment group,quizartinib treatment group,and dobutamine combined with quizartinib treatment group.Cell viability,ROS levels,and apoptosis rate were detected by CCK-8,Flow cytometry,respectively,as well as the expression of YAP1 protein by Western blot.Results:Both dobutamine and quizartinib inhibited the proliferation of FLT3-ITD mutant AML cell lines.Compared with the control group,the dobutamine group exhibited a significant increase in ROS levels(P＜0.01),an increase in apoptosis rates(P＜0.05),and a decrease in YAP1 protein expression(P＜0.05).Compared with the dobutamine group,the combination of quizartinib and dobutamine significantly reduced cell viability(P＜0.05),increased ROS levels(P＜0.01),and decreased YAP1 expression(P＜0.05).Conclusion:Dobutamine as a monotherapy can inhibit the proliferation of FLT3-ITD mutated AML cells,inducing apoptosis.Additionally,the combination of quizartinib enhances the targeted inhibitory effect on FLT3-ITD mutated AML.The mechanism may involve the inhibition of YAP1 protein expression in AML cells of this type,leading to an increase in ROS levels and exerting its anti-tumor effects.
