[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]

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":null,"pages":null},"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. 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\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"中国实验血液学杂志\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.19746/j.cnki.issn.1009-2137.2024.04.015\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"中国实验血液学杂志","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.19746/j.cnki.issn.1009-2137.2024.04.015","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Medicine","Score":null,"Total":0}
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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
[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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
中国实验血液学杂志
中国实验血液学杂志 Medicine-Medicine (all)
CiteScore
0.40
自引率
0.00%
发文量
7331
期刊介绍:
期刊最新文献
[Effect and Influencing Factors of Peripheral Blood Hematopoietic Stem Cells Collection from Unrelated Donors]. [Effect of Endothelial Activation and Stress Index(EASIX) on Prognosis of Peripheral T-Cell Lymphoma Patient]. [Effect of JMJD3-IRF4 Signaling Pathway-Mediated Macrophage Polarization on the Malignant Biological Behavior of Multiple Myeloma Cells]. [Effect of Tumor Suppressor Gene Kmt2c Heterozygous Deletion on Hematopoietic System in Mice]. [Effects of ATG5 and ATG7 Knockout on Ferroptosis Sensitivity of RPMI-8226 Cells].
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1