Apoptosis of renal carcinoma cells induced by NS398 via inhibiting prostaglandin E2

Objective: To investigate the expression of cyclooxygenase-2(COX-2) in renal carcinoma cells,and to explore the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the proliferation of renal carcinoma cells by detecting the effect of NS398,a selective inhibitor of COX-2,in renal carcinoma cells. Methods: Human renal cell carcinoma(RCC) cell line 786-0 was cultured with standard technique and treated with 25,50,100,150,and 200 μmol/L of NS398,respectively. The effect of NS398 on the proliferation of 786-0 cells was detected by MTT assay after the administration of NS398 for 24 and 48 hours. The apoptosis,the level of prostaglandin E2 (PGE2),and the expression of COX-2 in 786-0 cells after the administration of NS398 for 24 hours were determined by flow cytometry,enzyme immunoassay,and Western blotting,respectively. Results: NS398 inhibited the proliferation of 786-0 cells in a time- and concentration-dependent manner (P 0.05). A typical,subdiploid,apoptotic peak appeared before G0/G1 stage after the administration of NS398 for 24 hours,and the peak increased with the concentration of NS398 (P 0.05). NS398 significantly inhibited the release of PGE2 in 786-0 cells in a dose-dependent manner (P 0.05). The expression of COX-2 significantly decreased after the administration of NS398. Conclusion: NS398 could inhibit the proliferation of 786-0 cells by inducing the apoptosis. The possible mechanism includes down-regulating the expression of COX-2 and reducing the synthesis of PGE2 and thus inhibiting the proliferation of 786-0 cells induced by PGE2.