Inducing Apoptosis And Cooperating Chemotherapeutic Effect Of Celecoxib-specific Inhibitor Of COX-2 On Human Hepatoma Cells In Vitro

AIM:The current studies were designed to study the effects of inhibiting proliferation and inducing apoptosis of celecoxib on human hepatoma SMMC-7721 cells and gastric cancer SGC-7901 cells and the cooperating chemotherapeutic effect of celecoxib on the former cells in vitro. After oberserving the inhibitive and inducing effects of celecoxib at various concentrations and the cooperating chemotherapeutic effect with diffirent drugs, we discussed the mechanism behind those phenomena of specific inhibitor of COX-2 in favor of clinical practice primarily.METHODS:1 Through counting method to set out growth curve of SMMC-7721 ceils, and understand its basic characteristic.2 The two carcinoma cells were cultured with celecoxib at various concentrations (0,20,40, 80,160&320umol/L). Growth suppression was detected by MTT colorimetric assay, cell apoptotic alterations were evaluated by transmission electron microscopy (TEM) and flow cytometry (FCM).3 The carcinoma cells were cultured with fluorouracil (0.00001, 0.0001, 0.001, 0.01, 0.1, 1, 10, 100, 1000, 10000 g/m L), doxorubicin (0.02, 0.039, 0.078, 0.156, 0.313, 0.625, 1.25, 2.5, 5, 10 g/m L), and cisplatin (0.39, 0.78, 1.56, 3.13, 6.25,12.5, 25, 50, 100, 200 g/m L) at various concentrations. Andcelecoxib(80umoL/L) was also administrated. Growth suppression was detected by MTT colorimetric assay, and cell apoptotic alterations were evaluated by transmission electron microscope (TEM) and flow cytometry (FCM).4 The carcinoma cells were cultured with celecoxib(80umoL/L), and had been stained by H-E, Hoechst33258 and immunocytochemical method.RESULTS:1 Through counting method to set out growth curve of SMMC-7721 cells.2 The inhibition of proliferation on two carcinoma cells can be observed. And the inhibitive effect was dose-dependent. Apoptotic cells were observed by TEM and FCM.3 The cooperating chemotherapeutic effect of celecoxib on hepatoma cells could be observed (when celecoxib was 80 moI/L, fluorouracil was 0.00001mg/L, doxorubicin was 0.039mg/L and cisplatin was 0.39mg/L, the increasing inhibitive ratios were 12.3%, 31.8% and 82.8%, respectively). It was dose-dependent. Apoptotic cells were observed by TEM and FCM.4 By H-E, we observed acidophilic stain of cells. By stain of Hoechst33258, we also observed apoptosis. And by immunocytochemical method, we found quantity of COX-2 among cells had decreased obviously after disposing.CONCLUSION:1 Celecoxib inhibits proliferation , induces apoptosis of human twocarcinoma cells in vitro, and this effect is not only dose-dependent, but also heterogenous.2 Celecoxib can intensify the chemotherapeutic effect on carcinoma cells by cooperating drugs, and it is also heterogenous.3 The quantity of COX-2 in cells decreased obviously after disposing by celecoxib.