The Effective Mechanism Of Cyclooxygenase-2 In Oncogenesis And Progression Of Human Gastric Cancer

Objective: The study was intend to investigate the role of COX-2 in oncogenesis and progression of gastric carcinoma, and to explore the effects of aspirin on cell proliferation of human gastric cancer cell line SGC-7901 and its mechanism in vitro.Methods: Using MTT method, Flow Cytometry (FCM), 3H-TdR incorporation and electron microscopy, the effects of aspirin on the SGC-7901 of proliferation and its mechanism were assayed. By means of the technique using terminal deoxynucleotidly transferase mediated nick labelling, histochemistry and immunohistochemistry methods, the COX-2 expression , cell proliferation activity and apoptosis degree , VEGF expression and MVD were examined in 43 gastric carcinoma and 20 superficial gastritis.Results The data showed that the growth of SGC-7901 was inhibited by aspirin. The inhibitory rates for growth of SGC-7901 were positively correlated with the concentration and duration of aspirin in the media. ASA could inhibit DNA syntheses by 3H-TdR incorporation. Sub-G1 peak wasdetected by FCM, with the ratio of apoptosis being 7.8%-34. 38%. The cell percent of S and G2/M were increased , and that of Go/G] phase decreased after treatment in dose-dependent manner. The SGC-7901 exhibited some morphologic features of apoptosis, including cell shrinkage, nuclear condensation, DNA fragmentation and formation of apototic bodies by electron microscopy. The COX-2 expression in the tumorous tissue was remarkably higher than that in gastritis tissue. The expression of COX-2 in gastric carcinoma was related to clinical stage and lymph node metastasis (P<0.05) , but it had no connection with the size of tumor, depth of invasion and degree of differentiation (P>0.05).The apoptotic index decreased and PCNA index increased of gastric cancer cells were significantly correlated with the expression of COX-2.The COX-2, VEGF expression were closely correlated with MVD in gastric cancer.Conclusion: Aspirin inhibited the growth of human gastric cancer cell line SGC-7901 in vitro. The effect of the aspirin on phases of cell cycle and inducing apoptosis may be partially explained by the cytotoxic effects of aspirin. The expression of COX-2 may play a role in oncogenesis and progression of gastric carcinoma. The COX-2 inhibitor may be a novel, which is useful chemoprevention agents for human gastric cancer.