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Combination of celecoxib and calyculin-A inhibits epithelial-mesenchymal transition in human oral cancer cells.
Biotechnic & Histochemistry ( IF 1.6 ) Pub Date : 2020-01-15 , DOI: 10.1080/10520295.2019.1700429
Bharath Kumar Velmurugan,Chun-Hung Hua,Ming-Hsui Tsai,Chi-Pin Lee,Chia-Min Chung,Ying-Chin Ko

Expression of cyclo-oxygenase-2 (COX-2) and protein phosphatase 2A (PP2A) deactivation occurs frequently in oral squamous cell carcinoma (OSCC). We initially assessed COX-2 and PP2A protein expression in OSCC specimens using immunohistochemical (IHC) staining and western blot analysis. We found strong COX-2 and phosphorylated PP2A (p-PP2A) expression in OSCC samples. No significant difference in total PP2A expression was observed between cancer and nontumor tissues. The effect of combining COX-2 inhibitor and celecoxib (CXB) with the PP2A inhibitor, calyculin-A (CLA) on the OSCC cell line, HSC3, was evaluated in vitro. We found that a combination of 1 nM CLA and 50 µM CXB significantly inhibited cell viability, and migration and invasion of HSC3 cells. Western blots for AKT, p-AKT, ERK, p-ERK, E-cadherin, vimentin and β-catenin were conducted after treatment with CXB and/or CLA. Increased E-cadherin and decreased β-catenin expression were found in CXB or CLA treated hsc-3 cells, whereas the combined CXB and CLA treatment showed no difference in E-cadherin or β-catenin expression. Our findings suggest that CLA alone was more effective than CXB alone, but not in the combined drug treatment.



中文翻译:

塞来昔布和calyculin-A的组合抑制人口腔癌细胞中的上皮-间质转化。

口腔鳞状细胞癌(OSCC)中经常发生环氧合酶2(COX-2)和蛋白磷酸酶2A(PP2A)失活的表达。我们最初使用免疫组化(IHC)染色和蛋白质印迹分析评估了OSCC标本中COX-2和PP2A蛋白的表达。我们在OSCC样品中发现了强大的COX-2和磷酸化的PP2A(p-PP2A)表达。在癌症和非肿瘤组织之间未观察到PP2A总表达的显着差异。体外评估了COX-2抑制剂和塞来昔布(CXB)与PP2A抑制剂calyculin-A(CLA)联合对OSCC细胞HSC3的影响。我们发现1 nM CLA和50 µM CXB的组合可显着抑制细胞活力以及HSC3细胞的迁移和侵袭。AKT,p-AKT,ERK,p-ERK,E-钙粘着蛋白,在用CXB和/或CLA处理后进行波形蛋白和β-连环蛋白。在CXB或CLA处理的hsc-3细胞中发现了E-钙粘蛋白的增加和β-catenin表达的降低,而CXB和CLA的联合处理在E-cadherin或β-catenin的表达中没有差异。我们的研究结果表明,单独使用CLA比单独使用CXB更有效,但在联合药物治疗中无效。

更新日期:2020-01-15
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