Effects of ERK1/2 Inhibitors on the Growth of Acute Leukemia Cells.

IF 1.6 4区医学 Q4 ONCOLOGY

Anticancer research Pub Date : 2024-12-01 DOI:10.21873/anticanres.17354

Mai Itoh, Shuji Tohda

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引用次数: 0

Abstract

Background/aim: Extracellular signal-regulated kinases (ERK)1/2 are important regulatory proteins that control cell proliferation and survival, playing a significant role in cancer progression, metastasis, and chemoresistance. This study investigated the effects of ERK1/2 inhibitors on the in vitro growth of acute leukemia cell lines.

Materials and methods: Three ERK1/2 inhibitors were used: SCH772984, temuterkib (LY3214996), and ulixertinib (BVD-523). Four acute myeloid leukemia cell lines (OCI/AML3, HL-60, THP-1, and U-937) and two T-lymphoblastic leukemia cell lines (Jurakt and KOPT-K1) were treated with these inhibitors. Cell growth was assessed using a colorimetric assay, and cell-cycle progression and apoptosis were analyzed using flow cytometry. The expression of intracellular signaling proteins was evaluated via immunoblotting. The effects of small interfering RNA (siRNA)-mediated ERK1/2 knockdown were also evaluated.

Results: The inhibitors suppressed the growth of three leukemia cell lines (OCI/AML3, HL-60, and THP-1) harboring neuroblastoma rat sarcoma virus (NRAS) mutations. Growth suppression occurred through G0/G1 arrest in all three cell lines and through apoptosis in OCI/AML3 cells. Immunoblotting demonstrated that these inhibitors suppressed the expression of MYC proto-oncogene, bHLH transcription factor (MYC), in the three cell lines. The additional molecular mechanisms of growth suppression varied depending on the specific inhibitor and cell line. The inhibitors had milder suppressive effects on normal lymphocytes compared to the leukemia cell lines.

Conclusion: ERK1/2 inhibitors may serve as novel molecular-targeted drugs for treating leukemia with NRAS mutations.

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ERK1/2抑制剂对急性白血病细胞生长的影响。

背景/目的：细胞外信号调节激酶（Extracellular signal-regulated kinase， ERK）1/2是控制细胞增殖和存活的重要调控蛋白，在肿瘤的进展、转移和化疗耐药中起重要作用。本研究探讨ERK1/2抑制剂对急性白血病细胞系体外生长的影响。材料和方法：使用3种ERK1/2抑制剂：SCH772984、temuterkib （LY3214996）和ulixertinib （BVD-523）。四种急性髓系白血病细胞系（OCI/AML3、HL-60、THP-1和U-937）和两种t淋巴母细胞白血病细胞系（Jurakt和KOPT-K1）用这些抑制剂治疗。使用比色法评估细胞生长，使用流式细胞术分析细胞周期进展和凋亡。免疫印迹法检测细胞内信号蛋白的表达。我们还评估了小干扰RNA （siRNA）介导的ERK1/2敲低的作用。结果：这些抑制剂抑制了三种携带神经母细胞瘤大鼠肉瘤病毒（NRAS）突变的白血病细胞系（OCI/AML3、HL-60和THP-1）的生长。生长抑制发生在所有三种细胞系的G0/G1阻滞和OCI/AML3细胞的凋亡。免疫印迹显示，这些抑制剂抑制了MYC原癌基因bHLH转录因子（MYC）在三种细胞系中的表达。生长抑制的其他分子机制取决于特定的抑制剂和细胞系。与白血病细胞系相比，抑制剂对正常淋巴细胞的抑制作用较轻。结论：ERK1/2抑制剂可作为治疗NRAS突变白血病的新型分子靶向药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.