Abstract:AIM: To investigate the molecular mechanism by which columbianadin (CBN) exerts its antitumor effects in retinoblastoma (RB). METHODS: Y79 and WERI-Rb-1 cells were used for in vitro assays. Cell viability under different concentrations of CBN was assessed. The effects of CBN on RB cell behaviors were examined. In vivo, the antitumor efficacy of CBN was evaluated using a xenograft tumor model in BALB/c nude mice. Bioinformatic analysis was performed to predict potential molecular targets of CBN. The role of DNA topoisomerase II alpha (TOP2A) in activating the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was further explored. RB cells were infected with a lentivirus to overexpress TOP2A or treated with a PI3K/AKT inhibitor to analyze cellular behavior. A xenograft model was established using Y79 cells overexpressing TOP2A to validate the in vitro findings under CBN treatment. RESULTS: CBN inhibited proliferation, migration, and invasion, and promoted apoptosis of Y79 and WERI-Rb-1 cells. In vivo, CBN markedly reduced tumor growth in nude mice. TOP2A was highly expressed in RB cells, and its expression was downregulated by CBN treatment. Mechanistically, TOP2A promoted the malignant behavior of RB cells and tumor growth by activating the PI3K/AKT pathway. CONCLUSION: CBN inhibits RB progression by downregulating TOP2A protein expression, thereby blocking activation of the PI3K/AKT signaling pathway. These findings suggest that CBN could be a viable therapeutic candidate for treating RB.
