Experimental Studies on Cyclooxygenase-2 Inhibitor Induced Cervical Cancer Hela Cell Apoptosis and Its Molecular Mechanism

摘要

Objective To investigate the Hela cells growth inhibition and apoptosis possible molecular mechanisms. Methods Hela cells were treated with various concentrations (100 μmol/L,200 μmol/L, 300 μmol/L,400 μmol/L) of NS-398 (selective for COX-2 inhibition). Cell growth was measured by MTT (Thiazolyl blue). Apoptosis was detected by double staining flow cytometry (FCM). Levels of PGE_2 were measured by radioimmunoassay. The expressions of COX-2 protein were also examined by Western blot analysis. Results After treated with different concentrations of NS-398, the growth of Hela cells was suppressed significantly in a dose-and time-dependent manner (P < 0.01). The NS-398 can induce apoptosis with the apoptosis rates at 8.53%-43.46% by FCM in a dose-dependent manner. The release of PGE_2 was reduced in Hela cells with the values of 69.26 ± 2.13, 47.46 ± 2.18, 28.15 ± 1.64 and 17.01 ± 1.12, respectively, there was significant difference compared with control group (83.78 ± 1.11) (P < 0.01). The NS-398 could inhibit the activity and expression of COX-2 in a dose-dependent manner and down-regulated the expression of COX-2 protein greatly. Conclusions NS-398 could inhibit the proliferation and increase apoptosis in human Hela cells. These effects may be depended on the inhibition of the expression of COX-2 and PGE_2 by NS-398.