Effects of COX-2 selective inhibitor combined with Oxaliplatin on cells' proliferation and apoptosis of HCT-8 cells of colorectal carcinoma

【Objective】To observe the role of cyclooxygenase-2(COX-2) selective inhibitor NS-398 combined with Oxaliplatin(L-OHP) in human colorectal carcinoma HCT-8 cell line on proliferation and apoptosis. The antitumor effect of NS-398 combined with L-OHP and L-OHP alone on HCT-8 cells were compared.【Methods】The inhibition rate of HCT-8 cells treated by different concentration of L-OHP(1.25, 2.50, 5.00, 10.00 and 20.00μmol/L) alone and L-OHP combined with NS-398(20 and 80 μmol/L) for 24 h was detected by CCK-8 kit. Flow cytometry, Hoechst33258 staining and spectrophotometric assay were also used to analyze early apoptotic rate, apoptotic morphological changes and Caspase-3 activity, respectively.【Results】Cell proliferation assay showed that L-OHP and NS-398 had a dose-dependent inhibition effects on HCT-8 cells, respectively(P 0.05). The inhibition rate in NS-398 combined with L-OHP group was higher than that of the same concentration of L-OHP group, and as the dosage of NS-398 increasing, the inhibition effects increased. The apoptosis inducing effects in combined treatment group on HCT-8 cells were significantly higher than that of L-OHP group, the two drugs had a synergistic effect. Both of NS-398 and L-OHP could increase caspase-3 activity. Caspase-3 activity in the combined treatment group was significantly higher than that of L-OHP group and/or NS-398 group(P 0.01).【Conclusions】Both of NS-398 and L-OHP could inhibit HCT-8 cell proliferation and induce apoptosis. NS-398 could significantly enhance the ef-fects of L-OHP on HCT-8 cells.