Comparative Functional Effects of Abemaciclib and Arcyriaflavin A in MYCN-Amplified and Non-Amplified Neuroblastoma...

Cyclin-dependent kinase (CDK) inhibitors are promising therapeutic agents for neuroblastoma, particularly in MYCN-amplified tumors; however, the molecular responses associated with CDK inhibition remain incompletely understood. MYCN-amplified BE(2)-C and MYCN-non-amplified SH-SY5Y neuroblastoma cells were treated with Abemaciclib or Arcyriaflavin A. Drug responses were evaluated using MTT, Annexin V ELISA, wound healing, colony formation, quantitative real-time PCR, and Western blot analyses. Exploratory transcriptomic profiling was performed by RNA sequencing. Because only one biological replicate was available per condition, transcriptomic analyses were limited to descriptive expression trends and pathway-oriented interpretation rather than statistical differential expression analysis. Both inhibitors reduced cell viability in a dose- and time-dependent manner, with BE(2)-C cells showing greater sensitivity than SH-SY5Y cells. Treatment also increased Annexin V levels, reduced wound closure, impaired clonogenic growth, and decreased CDK4/CDK6 expression, as confirmed by qRT-PCR and Western blotting. Exploratory transcriptomic profiling identified concordant expression trends in genes associated with cell-cycle regulation, DNA replication, and mitotic progression, with broader pathway modulation observed in MYCN-amplified cells. Overall, CDK inhibition suppresses proliferation-associated phenotypes in neuroblastoma and is accompanied by exploratory transcriptomic changes that identify candidate pathways for future validation and mechanistic investigation of MYCN-associated therapeutic responses.