Induction of apoptosis with non-steroidal anti-inflammatory drugs NS398 in renal cell carcinoma and the mechanism

Objective To evaluate the effect of NS398,a selective cyclooxygenase-2 (COX-2) inhibitor,on cellular proliferation and apoptosis of human renal cell carcinoma (RCC) cell line,and to ex- amine the possible mechanism responsible for the anti-proliferative effects of NS398.Methods Human RCC cell line 786-0 was cultured by using standard technique and treated with NS398 at doses of 25,50, 100,150 and 200μmol/L respectively.Cellular inhibition was measured by MTT at 24 and 48 h.Apoptosis was evaluated by flow cytometry.Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the expression of COX-2 and bcl-2 mRNA and protein.Results NS398 sig- nificantly inhibit the cell growth of the 786-0 cells in a time- and concentration-dependent manner (P0.05).NS398 inhibited proliferation of 786-0 cells,along with the induction of apoptosis in a dose-depend- ent manner (P0.05).COX-2 and bcl-2 were significantly decreased by NS398 both at mRNA and pro- tein levels.Conclusion Overexpression of COX-2 exists in human 786-0 RCC cell line.NS398 can sup- press the proliferation of 786-0 RCC cells by inducing apoptosis.The possible mechanism is that NS398 in- hibits the expression of COX-2,resulting in the activity suppression of anti-apoptosis of bcl-2.NS398 may be a potentially effective agent against human RCC.