Lin Deng1,2, Ding-Qing Feng1, Bin Ling1,2. 1. China-Japan Friendship Hospital, Beijing 100029, China. 2. Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
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.
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.
Entities:
Keywords:
Ovarian cancer (OC); Cyclooxygenase-2 (COX-2); Drug resistance; Migration; Epithelial-mesenchymal transition (EMT)
Authors: Wilma Neumann; Brenda C Crews; Menyhárt B Sárosi; Cristina M Daniel; Kebreab Ghebreselasie; Matthias S Scholz; Lawrence J Marnett; Evamarie Hey-Hawkins Journal: ChemMedChem Date: 2014-10-15 Impact factor: 3.466
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