多巴酚丁胺增强Quizartinib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 Quizartinib on FLT3-ITD Mutant Acute Myeloid Leukemia].
发表日期:2024 Aug
作者:
Yu-Ang Gao, Qian-Yu Zhang, Xin Li, Shen-Yu Wang, Ji-Hui Li, Yang Xue, Chang-Yan Li, Hong-Mei Ning
来源:
Cellular & Molecular Immunology
摘要:
观察多巴酚丁胺对FLT3-ITD突变型急性髓系白血病(AML)细胞增殖的抑制作用,探讨多巴酚丁胺单药或联合奎扎替尼治疗该类AML的可行性。FLT3-ITD突变型细胞系体外培养MOLM13和MV4-11,分为对照组、多巴酚丁胺治疗组、奎扎替尼治疗组、多巴酚丁胺联合奎扎替尼治疗组。分别采用CCK-8、流式细胞仪检测细胞活力、ROS水平和凋亡率,并采用Western blot检测YAP1蛋白的表达。多巴酚丁胺和奎扎替尼均抑制FLT3-ITD突变型AML细胞系的增殖。与对照组相比,多巴酚丁胺组ROS水平显着升高(P < 0.01),细胞凋亡率升高(P < 0.05),YAP1蛋白表达降低(P < 0.01),YAP1表达降低(P < 0.05)。多巴酚丁胺单药可抑制FLT3-ITD突变的AML细胞增殖,诱导细胞凋亡。此外,quizartinib的组合增强了对FLT3-ITD突变AML的靶向抑制作用。其机制可能涉及抑制此类AML细胞中YAP1蛋白的表达,导致ROS水平升高,发挥抗肿瘤作用。
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.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.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 < 0.01), and decreased YAP1 expression (P < 0.05).Dobutamine as a monotherapy can inhibit theproliferation 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.