Epirubicin Induces Cell Cycle Arrest in Multiple Myeloma Cells by Downregulating CDC20 Expression

Although epirubicin is used among therapeutic options for multiple myeloma (MM), its clinical use remains limited, in part because the subgroup of patients most likely to benefit has not been clearly defined. Identifying robust biomarkers capable of predicting chemosensitivity is therefore essential to aimed personalized treatment strategies and enhance therapeutic outcomes. This study sought to characterize the molecular effects of epirubicin in MM cells, elucidate its tumor-suppressive mechanisms, and determine potential indicators for patient stratification.

The half-maximal inhibitory concentration (IC50) for epirubicin was quantified using the Cell Counting Kit-8 (CCK-8) viability assay. Gene expression alterations before and after epirubicin exposure were investigated via microarray profiling, followed by bioinformatic interrogation of publicly available datasets to examine the prognostic value of CDC20 expression in MM. Subsequently, functional validation was performed through in vitro assays and in vivo xenograft models to evaluate the impact of epirubicin on cell-cycle progression and tumor growth.

Epirubicin exhibited an IC50 of 23.85 μM in MM.1R cells. Transcriptome analysis revealed 115 genes upregulated and 25 genes downregulated post-treatment. Among the significantly altered genes were CDC20 (log FC = -2.409), KIF20A (log FC = -1.693), FAM72A (log FC = -1.742), CCNB1 (log FC = -1.787), PIF1 (log FC = -2.201), and LMNB1 (log FC = -1.589). Higher CDC20 expression was associated with shorter overall survival (OS), event-free survival (EFS), and post-progression survival (PPS). Mechanistic studies demonstrated that epirubicin triggers G2/M arrest in MM cells by suppressing CDC20, and in vivo experiments corroborated that decreased CDC20 expression contributes to reduced tumor proliferation via cell-cycle blockade.

Epirubicin exerts anti-myeloma effects by downregulating CDC20 and inducing cell-cycle arrest in MM, highlighting CDC20 as a potential biomarker for identifying MM patients likely to benefit from epirubicin.