Regulation of cell growth by selective COX-2 inhibitors in oral carcinoma cell lines

Abstract

Evidence indicates that NSAIDs that inhibit prostaglandin (PG) synthesis can reduce the incidence of colorectal cancers and that inhibition of cyclooxygenase-2 (COX-2) may be the underlying mechanism. The objective of this study was to investigate this putative mechanism by examining the effect of selective COX-2 inhibitors (Celebrex, DFU, NS-398) and COX-1 inhibitors (Aspirin) on the growth of two human oral carcinoma cell lines (OEC-M1 and KB) and one normal fibroblast cell line (NF). We found that the growth of OEC-M1 cells could be significantly inhibited by DFU concentrations above 30 μM (31%) after 4 days, and above 50 μM (35%) after 2 days in culture; by Celebrex at concentrations above 20 μM (52%) after 6 days, above 30 μM (36%) after 5 days, and above 40 μM (33%) after 4 days in culture; and by NS-398 above 1 μM (30%) after 6 days, and above 10 μM (35%) after 5 days in culture. The growth of KB cells could be significantly inhibited by DFU concentrations above 10 μM (33%) after 6 days, above 20 μM (35%) after 4 days in culture; and by Celebrex at concentrations above 10 μM (33%) after 5 days, and above 50 μM (30%) after 4 days in culture; and by NS-398 above 1 μM (45%) after 5 days, above 20 μM (36%) after 4 days in culture. The growth of NF cells could be significantly inhibited by DFU above 30 μM (45%) after 6 days, and above 40 μM (32%) after 3 days in culture, and by Celebrax at concentrations above 10 μM (42%) after 6 days, above 30 μM (31%) after 4 days, above 50 μM (32%) after 3 days in culture, and by NS-398 above 0.1 μM (35%) after 4 days, and above 1 μM (32%) after 3 days in culture. The growth-inhibitory concentration (IC 50) values for DFU on OEC-M1, KB, and NF cells were about 39.1, 14.8, and 42.9 μM at 144 h, respectively, and on KB was about 45.2 μM at 120 h. The IC 50 values for Celebrex on OEC-M1, KB, and NF cells were about 19.1, 8.6, and 15.8 μM at 144 h, respectively, and on KB and NF were about 27.7 and 35.3 μM, respectively, at 120 h. The IC 50 values for NS-398 on OEC-M1, KB, and NF were about 18.9, and 0.7 1 μM, respectively, at 144 h; on KB and NF values were about 10.8 and 1.4 μM, respectively, at 120 h and on KB and NF were about 26.6 and 4.1 μM, respectively, at 96 h. The results show that the growth of these cell lines is inhibited by three COX-2 selective inhibitors but not by any COX-1 selective inhibitors. These findings suggest that COX-2 may play an important role in the generation of biochemical mediators that stimulate the growth of human oral cancer and normal fibroblast cell lines.