TAZ Regulates the Cisplatin Resistance of Epithelial Ovarian Cancer Cells via the ANGPTL4/SOX2 Axis.

IF 2.6 4区医学 Q3 CELL BIOLOGY

Analytical Cellular Pathology Pub Date : 2022-09-22 eCollection Date: 2022-01-01 DOI:10.1155/2022/5632164

Caihong Li, Qin Wang, Youzhen Luo, Juan Xiang

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引用次数: 1

Abstract

Objective: Epithelial ovarian cancer (EOC) is a fatal gynecological malignancy. This study explored the mechanism of TAZ in regulating drug sensitivity of cisplatin (DDP-)-resistant EOC cells through the ANGPTL4/SOX2 axis.

Methods: The A2780/DDP cells were prepared by stepwise progressive concentration method. The drug resistance and TAZ expression in EOC cells were determined. Drug sensitivity was measured after TAZ overexpression in A2780 cells and TAZ downregulation in A2780/DDP cells, respectively. The effects of TAZ knockdown on apoptosis rate, stemness, and cancer stem cell (CSC) marker (CD44, OCT4, and ALDH1A) levels in A2780/DDP and DDP-treated A2780/DDP cells were assessed. The binding of TAZ and ANGPTL4 was verified using ChIP-qPCR, and ANGPTL4 and SOX2 levels were determined. The effects of different combined treatments of TAZ, ANGPTL4, and SOX2 on drug sensitivity of A2780/DDP cells and DDP-treated A2780/DDP cells were evaluated.

Results: TAZ was upregulated in drug-resistant EOC cells. TAZ knockdown significantly increased the drug sensitivity of A2780/DDP cells, while TAZ overexpression markedly decreased the drug sensitivity of A2780 cells. TAZ silencing promoted apoptosis of drug-resistant EOC cells and inhibited cell stemness. TAZ targeted ANGPTL4 and TAZ silencing enhanced drug sensitivity of A2780/DDP cells by inhibiting ANGPTL4. ANGPTL4 overexpression elevated SOX2 expression, and SOX2 downregulation reduced the drug resistance and promoted the apoptosis of A2780/DDP cells.

Conclusion: TAZ regulates DDP sensitivity of drug-resistant EOC cells via the ANGPTL4/SOX2 axis.

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TAZ通过ANGPTL4/SOX2轴调控卵巢癌上皮细胞对顺铂的耐药性

目的:上皮性卵巢癌(EOC)是一种致命的妇科恶性肿瘤。本研究通过ANGPTL4/SOX2轴探讨TAZ调控顺铂(DDP-)耐药EOC细胞药物敏感性的机制。方法:采用逐步浓缩法制备A2780/DDP细胞。测定EOC细胞的耐药性和TAZ的表达。分别在A2780细胞中过表达TAZ和在A2780/DDP细胞中下调TAZ后测定药物敏感性。评估TAZ敲低对A2780/DDP和DDP处理的A2780/DDP细胞的凋亡率、干细胞性和癌症干细胞(CSC)标志物(CD44、OCT4和ALDH1A)水平的影响。通过ChIP-qPCR验证TAZ与ANGPTL4的结合，并测定ANGPTL4和SOX2的水平。观察TAZ、ANGPTL4和SOX2不同联合处理对A2780/DDP细胞及DDP处理的A2780/DDP细胞药物敏感性的影响。结果:TAZ在EOC耐药细胞中表达上调。TAZ敲低显著提高A2780/DDP细胞的药物敏感性，TAZ过表达显著降低A2780细胞的药物敏感性。TAZ沉默可促进耐药EOC细胞凋亡，抑制细胞干性。TAZ靶向ANGPTL4, TAZ沉默通过抑制ANGPTL4增强A2780/DDP细胞的药物敏感性。ANGPTL4过表达上调SOX2表达，SOX2下调降低A2780/DDP细胞耐药，促进细胞凋亡。结论:TAZ通过ANGPTL4/SOX2轴调控耐药EOC细胞对DDP的敏感性。

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来源期刊

Analytical Cellular Pathology ONCOLOGY-CELL BIOLOGY

CiteScore

4.90

自引率

3.10%

发文量

审稿时长

16 weeks

期刊介绍： Analytical Cellular Pathology is a peer-reviewed, Open Access journal that provides a forum for scientists, medical practitioners and pathologists working in the area of cellular pathology. The journal publishes original research articles, review articles, and clinical studies related to cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, immunopathology, and hematology.