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 inhibito-ry 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 per-formed 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 resis-tance 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 migra-tion 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 cisplat-in.
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