Çerçi Alkaç Burcu, Soyöz Mustafa, Kılıçaslan Ayna Tülay, Pehlivan Melek, Pirim İbrahim
Department of Medical Biology, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Turkiye.
Department of Medical Laboratory Techniques, Vocational School of Health Services, Izmir Katip Celebi University, Izmir, Turkiye.
FASEB J. 2025 Jul 15;39(13):e70760. doi: 10.1096/fj.202501315.
Neuroblastoma (NB), a common pediatric cancer, is often associated with poor prognosis due to resistance to conventional therapies. Abemaciclib, a selective inhibitor of CDK4/6, is known for its ability to block cell cycle progression and induce cell death in various cancer types. In this study, we explore its potential therapeutic impact on NB by assessing its effects on cell proliferation, apoptosis, and the regulation of microRNAs (miRNAs) that are related to NB progression. Antiproliferative effect of abemaciclib, doxorubicin, cisplatin, and temozolomide (TMZ) were detected by MTT method. Combinations of abemaciclib-doxorubicin, abemaciclib-cisplatin, and abemaciclib-TMZ were also investigated by applying IC50 doses of the drugs for 24 h. ELISA and flow cytometry were performed for apoptosis detection, and for cell cycle analysis, flow cytometry was used. The expression levels of eight apoptosis, threee tumor suppressors, two oncogenes, and nine cell cycle-related genes were analyzed by quantitative PCR. Moreover, the expression levels of five NB-related miRNAs were determined. IC50 doses of abemaciclib, doxorubicin, cisplatin, and TMZ were found to be 4.757, 1.958, 34.21, and 240.7 uM in the 24 h, respectively. The combination of the drugs increased apoptosis and decreased cell migration and colony formation rates. The highest expression level difference was observed in PUMA when control and dose groups were compared. Increased expression levels of hsa-mir-18a-5p and hsa-miR-124-3p were detected in all drug-treated groups compared to the control group. Our results highlight the potential of abemaciclib as a promising treatment strategy for NB, particularly when used in combination with other therapies to overcome resistance and improve clinical outcomes.
神经母细胞瘤（NB）是一种常见的儿科癌症，由于对传统疗法耐药，其预后往往较差。阿贝西利是一种选择性CDK4/6抑制剂，以其阻断细胞周期进程和诱导多种癌症类型细胞死亡的能力而闻名。在本研究中，我们通过评估阿贝西利对细胞增殖、凋亡以及与NB进展相关的微小RNA（miRNA）调控的影响，探讨其对NB的潜在治疗作用。采用MTT法检测阿贝西利、多柔比星、顺铂和替莫唑胺（TMZ）的抗增殖作用。还通过应用药物的IC50剂量处理24小时，研究了阿贝西利 - 多柔比星、阿贝西利 - 顺铂和阿贝西利 - TMZ的联合用药情况。采用ELISA和流式细胞术检测凋亡情况，流式细胞术用于细胞周期分析。通过定量PCR分析8种凋亡相关基因、3种肿瘤抑制基因、2种癌基因和9种细胞周期相关基因的表达水平。此外，还测定了5种与NB相关的miRNA的表达水平。发现阿贝西利、多柔比星、顺铂和TMZ在24小时的IC50剂量分别为4.757、1.958、34.21和240.7μM。联合用药增加了凋亡，降低了细胞迁移和集落形成率。当比较对照组和剂量组时，PUMA的表达水平差异最为显著。与对照组相比，在所有药物处理组中均检测到hsa - mir - 18a - 5p和hsa - miR - 124 - 3p的表达水平升高。我们的结果突出了阿贝西利作为一种有前景的NB治疗策略的潜力，特别是与其他疗法联合使用以克服耐药性并改善临床结果时。
