Effects of NS-398 on apoptosis of hepatic carcinoma SMMC-7721 and BEL-7402 cells and expression of survivin and PTEN

Objective:NS-398 is a specific inhibitor of cyclooxygenase-2(COX-2),which is associated with proliferation,differentiation,apoptosis and carcinogenesis. In the present study, we aimed to analyze the inhibitory effects of NS-398 on the proliferation and apoptosis of hepatoma cells in vitro. Methods:Hepatic carcinoma SMMC-7721 and BEL-7402 cells were cultured. They were treated with NS-398 0,25,50,75,and 100 μmol/L, respectively. Each concentration group was subdivided into three groups: treatment for 24, 48, and 72 h, respectively. The cells were harvested daily for 3 days. Growth inhibition of the two cell lines were measured by MTT assay. Cell cycle,apoptosis, and expression of COX-2, survivin, and PTEN (phosphatase and tension homology deleted from chromosome 10) were determined quantitatively by flow cytometry (FCM) analysis. Results: Compared with control group,NS-398 significantly inhibited the proliferation of SMMC-7721 and BEL-7402 cells. NS-398 also significantly decreased the proportion of cells in the G0/G1 phase and increased the proportion of cells in the G2/M phase but had so significant effects on the proportion of cells in S phase. The expressions of COX-2,survivin,and PTEN were significantly down-regulated in SMMC-7721 and BEL-7402 cells by NS-398. All the effects of NS-398 were in a dose- and concentration-dependent manner(P0.001). Conclusion:NS-398 inhibited the proliferation of SMMC-7721 and BEL-7402 cells by inducing apoptosis of the two cells. The effects may be due to the down-regulation of expression of survivin and PTEN.