Yu-Ang Gao, Qian-Yu Zhang, Xin Li, Shen-Yu Wang, Ji-Hui Li, Yang Xue, Chang-Yan Li, Hong-Mei Ning
{"title":"[多巴酚丁胺增强奎沙替尼对FLT3-ITD突变型急性髓性白血病的靶向抑制作用]","authors":"Yu-Ang Gao, Qian-Yu Zhang, Xin Li, Shen-Yu Wang, Ji-Hui Li, Yang Xue, Chang-Yan Li, Hong-Mei Ning","doi":"10.19746/j.cnki.issn.1009-2137.2024.04.015","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To observe the inhibitory effect of dobutamine on proliferation of <i>FLT3-ITD</i> 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.</p><p><strong>Methods: </strong><i>FLT3-ITD</i> 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.</p><p><strong>Results: </strong>Both dobutamine and quizartinib inhibited the proliferation of <i>FLT3-ITD</i> mutant AML cell lines. Compared with the control group, the dobutamine group exhibited a significant increase in ROS levels (<i>P</i> < 0.01), an increase in apoptosis rates (<i>P</i> < 0.05), and a decrease in YAP1 protein expression (<i>P</i> < 0.01), and decreased YAP1 expression (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>Dobutamine as a monotherapy can inhibit theproliferation of <i>FLT3-ITD</i> mutated AML cells, inducing apoptosis. Additionally, the combination of quizartinib enhances the targeted inhibitory effect on <i>FLT3-ITD</i> 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.</p>","PeriodicalId":35777,"journal":{"name":"中国实验血液学杂志","volume":"32 4","pages":"1071-1077"},"PeriodicalIF":0.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Dobutamine Enhances the Targeted Inhibitory Effect of Quizartinib on <i>FLT3-ITD</i> Mutant Acute Myeloid Leukemia].\",\"authors\":\"Yu-Ang Gao, Qian-Yu Zhang, Xin Li, Shen-Yu Wang, Ji-Hui Li, Yang Xue, Chang-Yan Li, Hong-Mei Ning\",\"doi\":\"10.19746/j.cnki.issn.1009-2137.2024.04.015\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To observe the inhibitory effect of dobutamine on proliferation of <i>FLT3-ITD</i> 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.</p><p><strong>Methods: </strong><i>FLT3-ITD</i> 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.</p><p><strong>Results: </strong>Both dobutamine and quizartinib inhibited the proliferation of <i>FLT3-ITD</i> mutant AML cell lines. Compared with the control group, the dobutamine group exhibited a significant increase in ROS levels (<i>P</i> < 0.01), an increase in apoptosis rates (<i>P</i> < 0.05), and a decrease in YAP1 protein expression (<i>P</i> < 0.01), and decreased YAP1 expression (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>Dobutamine as a monotherapy can inhibit theproliferation of <i>FLT3-ITD</i> mutated AML cells, inducing apoptosis. Additionally, the combination of quizartinib enhances the targeted inhibitory effect on <i>FLT3-ITD</i> mutated AML. 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引用次数: 0
摘要
目的观察多巴酚丁胺对FLT3-ITD突变急性髓性白血病(AML)细胞增殖的抑制作用,探讨多巴酚丁胺作为单药或与奎沙替尼联合治疗该类型AML的可行性:方法:体外培养FLT3-ITD突变细胞株MOLM13和MV4-11,将其分为对照组、多巴酚丁胺治疗组、喹唑替尼治疗组和多巴酚丁胺联合喹唑替尼治疗组。分别用CCK-8和流式细胞术检测细胞活力、ROS水平和凋亡率,并用Western blot检测YAP1蛋白的表达:结果:多巴酚丁胺和奎沙替尼都能抑制FLT3-ITD突变型AML细胞株的增殖。与对照组相比,多巴酚丁胺组ROS水平显著增加(P<0.01),细胞凋亡率增加(P<0.05),YAP1蛋白表达减少(P<0.01),YAP1表达降低(P<0.05):多巴酚丁胺单药治疗可抑制FLT3-ITD突变AML细胞的增殖,诱导细胞凋亡。结论:多布他明单药可抑制FLT3-ITD突变型AML细胞的增殖,诱导细胞凋亡,与喹沙替尼联合用药可增强对FLT3-ITD突变型AML的靶向抑制作用。其机制可能是抑制了该类型 AML 细胞中 YAP1 蛋白的表达,导致 ROS 水平升高,从而发挥抗肿瘤作用。
[Dobutamine Enhances the Targeted Inhibitory Effect of Quizartinib on FLT3-ITD Mutant Acute Myeloid Leukemia].
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 < 0.01), and decreased YAP1 expression (P < 0.05).
Conclusion: 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.