Antiproliferative and Apoptotic Effects of Mono/Combined Treatment of Abemaciclib and Regulation of Neuroblastoma-Related miRNAs

Abstract

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.