The HDAC6 inhibitor ACY-1215 enhances the anticancer activity of oxaliplatin in colorectal cancer cells

ACY-1215, also known as ricolinostat, is a leading histone deacetylase 6 inhibitor, which is currently being tested in clinical trials for hematological malignancies. Previous studies have reported that ACY-1215 is not potent enough as a monotherapy for the treatment of colorectal cancer (CRC), which generally requires combination therapy for successful treatment. Therefore, the present study aimed to determine whether the synergistic interaction detected between ACY-1215 and anticancer agents in hematological cancers could occur in solid tumors. The results of the present study indicated that ACY-1215 exerted a potent synergistic anti-proliferative effect when used in combination with anticancer agents in CRC cells. The combination of ACY-1215 and oxaliplatin was more potent than either drug alone, as indicated by an increase in apoptotic cells and their effects on the apoptotic pathway; ACY-1215 and oxaliplatin cotreatment activated caspase-3 and poly (ADP ribose) polymerase, increased B-cell lymphoma (Bcl)-2 homologous antagonist/killer expression, and decreased Bcl-extra large protein, phosphorylated-extracellular signal-regulated kinase and phosphorylated-protein kinase B expression. In addition, combined treatment of ACY-1215 and anticancer agents induced synergistic upregulation of programmed death-ligand 1. These findings suggested that a therapeutic strategy that combines ACY-1215 and oxaliplatin warrants attention for the treatment of solid tumors, including CRC.