【摘要】 目的：探讨ARPC1B通过Wnt/β-catenin信号通路对卵巢癌（OC）顺铂耐药的影响及其作用机制。方法：比较OC细胞（SKOV3）与卵巢癌耐药细胞（SKOV3/DDP细胞）对顺铂的半抑制浓度(IC₅₀)值以及ARPC1B的表达；构建稳定沉默ARPC1B的卵巢癌耐药细胞系，细胞计数试剂盒（CCK-8）检测敲低ARPC1B后SKOV3/DDP细胞对顺铂IC₅₀值，克隆形成实验、Transwell和划痕实验分别检测SKOV3/DDP细胞增殖和迁移能力，流式细胞术检测细胞凋亡，蛋白质免疫印迹法（western blotting）检测凋亡相关蛋白及Wnt/β-catenin信号通路关键分子蛋白表达水平的变化。结果：SKOV3/DDP细胞的耐药指数>2，且AR-PC1B在SKOV3/DDP细胞中高表达（P<0.05）。沉默ARPC1B后SKOV3/DDP细胞对顺铂的IC₅₀值下降，增殖和迁移能力减弱（P<0.05）;ARPC1B敲低组细胞中BAX和Cleaved-Caspase 3蛋白以及凋亡率显著升高，而Bcl-2、β-catenin、c-myc和cyclin D1蛋白表达水平降低（P<0.05）。结论：ARPC1B可能通过Wnt/β-catenin信号通路抑制SKOV3/DDP细胞凋亡，进而增强SKOV3/DDP细胞对顺铂的耐药性。更多还原

【Abstract】 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 IC₅₀values 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 IC₅₀values 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 SKOV3DDP cells through the Wnt/β-catenin signaling pathway,which in turn enhances the SKOV3/DDP cells to cisplatin.更多还原