Abstract
Objective
Drug-resistance and metastasis are major reasons for the high mortality of ovarian cancer (OC) patients. Cyclooxygenase-2 (COX-2) plays a critical role in OC development. This study was designed to evaluate the effects of COX-2 on migration and cisplatin (cis-dichloro diammine platinum, CDDP) resistance of OC cells and explore its related mechanisms.
Methods
Cell counting kit-8 (CCK-8) assay was used to detect the cytotoxicity effects of celecoxib (CXB) and CDDP on SKOV3 and ES2 cells. The effect of COX-2 on migration was evaluated via the healing test. Western blot and real-time quantitative polymerase chain reaction (qPCR) were used to analyze E-cadherin, vimentin, Snail, and Slug levels.
Results
COX-2 promoted drug-resistance and cell migration. CXB inhibited these effects. The combination of CDDP and CXB increased tumor cell sensitivity, reduced the amount of CDDP required, and shortened treatment administration time. COX-2 upregulation increased the expression of Snail and Slug, resulting in E-cadherin expression downregulation and vimentin upregulation.
Conclusions
COX-2 promotes cancer cell migration and CDDP resistance and may serve as a potential target for curing OC.
摘要
目 的
研究环氧合酶-2 (COX-2) 对卵巢癌细胞迁移和耐药性的影响及其机制.
创新点
本研究发现COX-2对卵巢癌发生发展有一定的促进作用, 可以通过上皮间质转化 (EMT) 途径促进卵巢癌细胞的迁移和顺铂 (CDDP) 耐药. 其抑制剂塞来昔布 (CXB) 能起到协同抗癌的效果.
方 法
CCK-8 检测 CXB 和 CDDP 对 SKOV3 和 ES2 细胞的毒性作用. 划痕实验评估 COX-2 对卵巢癌细胞迁移的作用. 蛋白质免疫印迹 (western blot) 和聚合酶链式反应 (PCR) 检测 EMT 相关基因和蛋白的表达水平.
结 论
COX-2 可以通过 EMT 促进卵巢癌细胞迁移和 CDDP 耐药; CXB 可以起到抑制作用, 与 CDDP 协同抗癌. COX-2 可以作为卵巢癌治疗的一个潜在靶点.
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Acknowledgments
The authors would like to thank Prof. Zhong-jun DONG and Dr. Juan DU (Tsinghua University, Beijing, China) for technical support.
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Lin DENG and Bin LING designed experiments. Lin DENG carried out experiments, analyzed experimental results, and wrote the manuscript. Bin LING and Ding-qing FENG revised the manuscript. All authors have read and approved the final manuscript, have full access to all the data in the study, and take responsibility for the integrity and security of the data.
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Lin DENG, Ding-qing FENG, and Bin LING declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
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Project supported by the National Natural Science Foundation of China (No. 81372777)
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Deng, L., Feng, Dq. & Ling, B. Cyclooxygenase-2 promotes ovarian cancer cell migration and cisplatin resistance via regulating epithelial mesenchymal transition. J. Zhejiang Univ. Sci. B 21, 315–326 (2020). https://doi.org/10.1631/jzus.B1900445
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DOI: https://doi.org/10.1631/jzus.B1900445
Key words
- Ovarian cancer (OC)
- Cyclooxygenase-2 (COX-2)
- Drug resistance
- Migration
- Epithelial-mesenchymal transition (EMT)