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
Dobutamine Enhances the Targeted Inhibitory Effect of Quizar-tinib on FLT3-ITD Mutant Acute Myeloid Leukemia
高宇昂 1张倩钰 2李欣 3王绅宇 3李芨慧 4薛阳 5李长燕 5宁红梅1
作者信息
- 1. 解放军医学院研究生院;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
- 2. 安徽医科大学解放军总医院第五医学临床学院,合肥 230032
- 3. 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
- 4. 中国人民解放军总医院第八医学中心超声科,北京 100091
- 5. 中国人民解放军军事科学院军事医学研究院辐射医学研究所,北京 100850
- 折叠
摘要
目的:观察多巴酚丁胺对人FLT3-ITD突变型急性髓系白血病(AML)细胞的增殖抑制作用,探讨多巴酚丁胺单药或者联合奎扎替尼治疗该型AML的可行性.方法:体外培养FLT3-ITD突变AML细胞系MOLM13及MV4-11,实验分为对照组、多巴酚丁胺处理组、奎扎替尼处理组、多巴酚丁胺联合奎扎替尼处理组,采用CCK-8法、流式细胞术分别检测各组细胞活性、细胞凋亡率及ROS水平,并通过Western blot检测YAP1蛋白的表达.结果:多巴酚丁胺和奎扎替尼均可抑制FLT3-ITD突变型AML细胞系MOLM13、MV4-11的增殖.与对照组相比,多巴酚丁胺组FLT3-ITD突变AML细胞的ROS水平显著上升(P＜0.01),凋亡率增加(P＜0.05),其YAP1蛋白的表达减少(P＜0.05);与多巴酚丁胺组相比,奎扎替尼联合多巴酚丁胺组的细胞活性显著降低(P＜0.05),ROS水平上升(P＜0.01),YAP1表达减少(P＜0.05).结论:多巴酚丁胺单药可抑制FLT3-ITD突变型AML细胞的增殖,引起其凋亡,且联合奎扎替尼可增强对FLT3-ITD突变型急性髓性白血病的靶向抑制作用.其机制可能是通过抑制该型AML细胞YAP1蛋白的表达,提高ROS水平从而发挥其抗肿瘤作用.
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.
关键词
急性髓系白血病/fms样酪氨酸激酶3/多巴酚丁胺/YAP1Key words
acute myeloid leukemia/fms-like tyrosine kinase 3/dobutamine/YAP1引用本文复制引用
出版年
2024
NETL
NSTL
万方数据