ARPC1B regulates cisplatin resistance in ovarian cancer through the Wnt/β-catenin signaling pathway
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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ARPC1B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 cyclinD1 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。
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关键词
- 卵巢癌 /
- ARPC1B /
- 顺铂耐药 /
- Wnt/β-catenin /
- 凋亡
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 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.-
Keywords
- ovarian cancer /
- ARPC1B /
- cisplatin resistance /
- Wnt/β-catenin /
- apoptosis
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