Cyclooxygenase-2 promotes ovarian cancer cell migration and cisplatin resistance via regulating epithelial mesenchymal transition  

环氧合酶-2(COX-2)通过调控细胞上皮间质转化(EMT)促进卵巢癌细胞迁移及其耐药性

作　　者：Lin DENG Ding-qing FENG Bin LING 

机构地区：[1]China-Japan Friendship Hospital,Beijing 100029,China [2]Graduate School of Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2020年第4期315-326,共12页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：Project supported by the National Natural Science Foundation of China(No.81372777)。

摘　　要：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(q PCR) 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.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。

关 键 词：Ovarian cancer(OC) Cyclooxygenase-2(COX-2) Drug resistance Migration Epithelial-mesenchymal transition(EMT) 

分 类 号：R737.31[医药卫生—肿瘤]