ARPC1B regulates cisplatin resistance in ovarian cancer through the Wnt/β-catenin signaling pathway

Objective: To investigate the effect of ARPC1B on cisplatin resistance in ovarian cancer (OC) through the Wnt/β-catenin signaling pathway and its mechanism of action. Methods: The half maximal inhibitory concentration (IC₅₀) values of OC cells (SKOV3) and drug-resistant OC cells (SKOV3/DDP cells) to cisplatin and the expression of ARPC1B were compared. Drug-resistant ovarian cancer cell lines with stable silencing of ARPC1B were constructed, and the IC₅₀ values of SKOV3/DDP cells to cisplatin after knockdown of ARPC1B were detected by cell counting kit- 8 (CCK- 8). Clone formation assay, Transwell and scratch assay were performed to determine the proliferation and migration capacities of SKOV3/DDP cells, respectively. The apoptosis was measured by flow cytometry, and apoptosis-associated proteins, as well as the protein expression levels of key molecules of the Wnt/β-catenin signaling pathway were tested by western blotting. Results: The drug resistance index of SKOV3/DDP cells was ＞2, and ARPC1B was highly expressed in SKOV3/DDP cells (P＜0.05). Silencing of ARPC1B decreased the IC₅₀ values of SKOV3/DDP cells to cisplatin, and the proliferation and migration capacities were weakened (P＜0.05). BAX and Cleaved-Caspase 3 proteins, as well as apoptosis rate were significantly increased in the cells of the ARPC1B knockdown group, while Bcl-2, β-catenin, c-myc and cyclin D1 protein expression levels were reduced (P＜0.05). Conclusion: ARPC1B may inhibit the apoptosis of SKOV3/DDP cells through the Wnt/β-catenin signaling pathway, which in turn enhances the SKOV3/DDP cells to cisplatin.