Parecoxib expresses anti-metastasis effect through inhibition of epithelial-mesenchymal transition and the Wnt/β-catenin signaling pathway in human colon cancer DLD-1 cell line.

Abstract

Colorectal cancer is the third leading cause of cancer death in Taiwan. Current treatments involve combination of surgical resection, radiation, and chemotherapy. These treatments have demonstrated to increased five-year survival of a patient with colorectal cancer. However, metastasis is a major capability of cancer cells that causes poor prognosis, recurrence, and even death. Epidemiological and clinical studies have suggested the use of non-steroidal anti-inflammatory drugs (NSAIDs) as an effective class of compounds to prevent colon cancer. Parecoxib is an NSAID and the only parenterally administered selective cyclooxygenase (COX)-2 inhibitor. In this study, we evaluated whether parecoxib inhibits the metastasis of DLD-1 human colon cancer cells, a COX-2 null cell line, and the underlying mechanism. Cell migration of the DLD-1 cells was significantly inhibited by parecoxib treatment as shown by the Transwell migration assay. This enhanced anti-migration effect was correlated with the attenuated phosphorylation of Akt, expression of vimentin (a mesenchymal marker), and β-catenin, and corresponded with the upregulated GSK3β and E-cadherin (an epithelial marker). These findings suggested that parecoxib could inhibit the epithelial-mesenchymal transition (EMT) and metastasis in human colon cancer cells by downregulating β-catenin. Thus, parecoxib could provide a novel prospective strategy for a combination treatment with chemotherapeutic drugs against metastasis of human colon cancer.