IKBKE 激酶抑制剂 MCCK1 对急性 B 淋巴细胞白血病细胞的影响。

IF 2.6 4区 工程技术 Q1 Mathematics Mathematical Biosciences and Engineering Pub Date : 2024-03-05 DOI:10.3934/mbe.2024228
Shuangshuang Wen, Peng Zhao, Siyu Chen, Bo Deng, Qin Fang, Jishi Wang
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引用次数: 0

摘要

B 细胞急性淋巴细胞白血病(B-ALL)是一种恶性血液疾病,对儿童和青少年的危害尤为严重,复发或无反应的病例在癌症相关死亡病例中占很大比例。IKBKE与先天性免疫、肿瘤促进和耐药性有关,但人们对IKBKE在B-ALL中的作用仍然知之甚少。因此,本研究旨在探索 IKBKE 抑制剂 MCCK1 对 B-ALL 细胞的影响。研究涵盖了多种实验,包括临床样本、体外和体内调查。定量实时荧光 PCR 和蛋白质印迹检测显示,B-ALL 患者体内 IKBKE mRNA 和蛋白质表达量增加。随后用 B-ALL 细胞系进行的体外实验表明,MCCK1 处理会导致细胞活力和存活率降低,流式细胞仪显示细胞周期停滞。使用 B-ALL 小鼠肿瘤模型进行的体内实验证实了 MCCK1 在抑制肿瘤增殖方面的功效。这些发现共同表明,B-ALL 患者体内升高的 IKBKE 可能是一个很有前景的药物靶点,MCCK1 在体外和体内都显示出诱导 B-ALL 细胞凋亡的潜力。
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The impact of MCCK1, an inhibitor of IKBKE kinase, on acute B lymphocyte leukemia cells.

B-cell acute lymphoblastic leukemia (B-ALL) is a malignant blood disorder, particularly detrimental to children and adolescents, with recurrent or unresponsive cases contributing significantly to cancer-associated fatalities. IKBKE, associated with innate immunity, tumor promotion, and drug resistance, remains poorly understood in the context of B-ALL. Thus, this research aimed to explore the impact of the IKBKE inhibitor MCCK1 on B-ALL cells. The study encompassed diverse experiments, including clinical samples, in vitro and in vivo investigations. Quantitative real-time fluorescence PCR and protein blotting revealed heightened IKBKE mRNA and protein expression in B-ALL patients. Subsequent in vitro experiments with B-ALL cell lines demonstrated that MCCK1 treatment resulted in reduced cell viability and survival rates, with flow cytometry indicating cell cycle arrest. In vivo experiments using B-ALL mouse tumor models substantiated MCCK1's efficacy in impeding tumor proliferation. These findings collectively suggest that IKBKE, found to be elevated in B-ALL patients, may serve as a promising drug target, with MCCK1 demonstrating potential for inducing apoptosis in B-ALL cells both in vitro and in vivo.

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来源期刊
Mathematical Biosciences and Engineering
Mathematical Biosciences and Engineering 工程技术-数学跨学科应用
CiteScore
3.90
自引率
7.70%
发文量
586
审稿时长
>12 weeks
期刊介绍: Mathematical Biosciences and Engineering (MBE) is an interdisciplinary Open Access journal promoting cutting-edge research, technology transfer and knowledge translation about complex data and information processing. MBE publishes Research articles (long and original research); Communications (short and novel research); Expository papers; Technology Transfer and Knowledge Translation reports (description of new technologies and products); Announcements and Industrial Progress and News (announcements and even advertisement, including major conferences).
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