H. Yamashita, M. Osaki, S. Honjo
Nov 1, 2003
BACKGROUND NS-398, a selective cyclooxygenase-2 (COX-2) inhibitor, has been shown to suppress cell proliferation and induce apoptosis in a variety of human cancer cell lines in vitro, except for sarcoma cell lines. The aim of this study was to examine the effect of NS-398 on two human malignant fibrous histiocytoma (MFH) cell lines: MFH-ino and MFH-ToE. MATERIALS AND METHODS We investigated the effect of NS-398 at various concentrations on the growth of MFH cell lines using cell proliferation assay, cell cycle analysis and EIA assay of PGE2 production. RESULTS Western blot analysis revealed COX-2 protein expression in both MFH cell lines. NS-398 at 10 or 100 microM resulted in inhibition of the cell proliferation in a dose- and time-dependent manner. NS-398 at 100 microM also induced G0/G1 arrest accompanied by up-regulation of P21WAF1 in MFH-ino cells in a time-dependent manner until 72 hours. NS-398 slightly increased the number of cells in the G2/M-phase and decreased the number in the G0/G1-phase in MFH-ToE cells lacking p53 gene function. Moreover, NS-398 down-regulated PGE2 production in the MFH-ToE cells in a time-dependent manner, but not in the MFH-ino cells. CONCLUSION Our results indicate that NS-398 inhibits the cell growth and induces G0/G1 arrest in MFH-ino cells accompanied with up-regulation of P21WAF1.