A selective cyclooxygenase-2 inhibitor, NS398, inhibits cell growth and induces cell cycle arrest in the G2/M phase in human esophageal squamous cell carcinoma cells.

It is well known that cyclooxygenase (COX) -2 is expressed in a variety of human malignant solid tumors, associated with tumor angiogenesis, cell proliferation and inhibition of apoptosis. Here, we examined the effect of NS398, a selective COX-2 inhibitor, on two human esophageal squamous cell carcinoma (SCC) cell lines, TE-1 and TE-12. Western blot analysis confirmed the expression of COX-2 in TE-12, but not in TE-1. Treatment with 100microM NS398 suppressed the cell viability in TE-12 (48.6% of control) after 48 hours, in contrast to showing no effects in TE-1. The apoptotic index was extremely low in both cell lines after the treatment. NS398 clearly increased the number of cells in the G2/M phase and decreased the cells in the G1 and S phases in TE-12, but not TE-1. A pre-G1 fraction was not noted in either cell line. Moreover, TE-12 cells showed a decrease in the expression levels of cyclin B1 and an increase in p27Kip1. These findings suggest that NS398 inhibits cell growth and induces G2/M arrest in human SCC cells expressing COX-2.