Combination of celecoxib and calyculin-A inhibits epithelial-mesenchymal transition in human oral cancer cells

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 mu M 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 beta-catenin were conducted after treatment with CXB and/or CLA. Increased E-cadherin and decreased beta-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 beta-catenin expression. Our findings suggest that CLA alone was more effective than CXB alone, but not in the combined drug treatment.