Celecoxib and Indomethacin Inhibit the Growth of Cancer and Oral Keratinocyte Cell Lines via Cyclooxygenase-2 Independent Mechanism / 대한이비인후과학회지

ABSTRACT

BACKGROUND AND OBJECTIVES: Overexpression of cyclooxygenase-2 (COX-2), a rate-limiting enzyme in the generation of prostanoids from arachidonic acid, has known to be closely related to tumorigenesis, tumor growth, angiogenesis, and metastasis. Selective or non-selective COX-2 inhibitors have been used for the growth inhibition of cancers with preventative intents ; however, it has been suggested recently that cancer cells have COX-2-independent mechanisms. MATERIALS AND METHOD: Using MTT assat and cell counts, we observed the growth inhibition of SCC VII, CT-26 and B16F10 murine cancer cell lines when treated by celecoxib and indomethacin. SNU-1041 and HOK 16B were used as controls for comparing with the murine cell lines. The COX-2 expression of these cell lines was analyzed by western blotting and compared with the degree of inhibition by the drugs. RESULTS: The growth inhibition of the cell lines by the drugs was clearly demonstrated in a concentration-dependent manner and depended on the type of cell lines and test drug. The in vitro viability assay revealed that CT-26 expressing COX-2 protein was slightly inhibited but SCC VII and B16F10 without COX-2 expression were moderate-to-highly inhibited by the drug treatment. Celecoxib and indomethacin appeared to have no close relation with the COX-2 expression of cell lines in their growth inhibition. HOK 16B showed a resistance by concentrations less than 25 microM of celecoxib, which implies that celecoxib has a more selective effect on tumor cells and is safer than indomethacin. CONCLUSION: The growth of cancer cells was inhibited by celecoxib and indomethacin treatment, which depends on the type of cancer, treated drug, and its concentration. Their suppressive effect is not closely related to the COX-2 expression of cancer cells.