Effects Of Cyclooxygenase-2 On The Proliferation And Apoptosis Of Gastric Carcinoma Cells

AIM:To study the effect of selective cyclooxygenase - 2(cox-2) inhibitor nimesulide on the proliferation of SGC-7901, the apoptosis in the gastric carcinoma tissues and the adjacent noncancerous tissues, the expression and their relationship of cox-2, Fas, FasL, bcl-2, bax, NF-KB, and the expression of bcl-2 and bax in SGC-7901, and the level of PGE2 in cultural supenatant in the groups with or without nimesulide treatment. To investigate the role and the potential mechanisms of cox-2 on the proliferation and apoptosis of gastric cells.Methods:1.The effect of nimesulide on the proliferation of SGC-7901 was measured by cell count and MTT assay.2. The apoptosis rate for gastric carcinoma tissues and the adjacent noncancerous tissues was detected by TUNEL.3.The expression of cox-2, Fas, Fasl, bcl-2, NF-KB and their relationship was demonstrated by S~P immunohistochemistry.4. The levels of bax and bcl-2 in SGC-7901 with or without nimesulide treatment were evaluted by flow cytometer.5. The level of PGE2 in cultural superatant with or without nimesulide treatment were measured by radioimmunoassay.Results:l.The proliferation of SGC-7901 was inhibited by different concentration of nimesulide in a time-dependent and dose-dependent manner, the highest survival rate of SGC-7901 was 78. 7% and the lowest was 22.7% with 72h treatment of nimesulide.2.The apoptosis rate for gastric carcinoma tissues(6.7±2.5%) was significantly lower than that for the adjacent noncancerous tissues(17. 5 ±3. 2%, p<0.05). The apoptosis rate for cox-2-positive gastric carcinoma tissues was significantly lower than that for cox-2-negative tissues(p<0.05).3. The expression of cox-2, FasL,bcl-2 and NF-KB in gastric carcinoma tissues was significantly higher than that in adjacent noncancerous tissues(p<0.05), whereas the expression of Fas and bax was significantly lower than that in adjacent noncancerous tissues(p<0.05). The expression of cox-2 was negatively correlated with the expression of Fas and bax (p<0.05) and positivly correlated with the expression of bcl-2 and NF-KB (p<0.05), whereas the expression of cox-2 seemed has no significantly relationship with the expression of FasL.4. The level of bax in SGC-7901 in nimesulide treated group was increased in a dose-dependent manner and the level of bcl-2 was decreased in the same manner.5.The level of PGE2 in cultural supenatant was obviously decreased with 24h treatment of nimesulide, and its level was negatively correlated with the nimesulide corcentration.CONCLUSION:1. Selective cox-2 inhibitor nimesulide inhibits the proliferation of SGC-7901 and cox-2 prompts the proliferation of SGC-7901.2. The apoptosis rate for gastric carcinoma tissues significantly decreased, cox-2 may inhibit the apoptosis of gastric carcinoma cells.3. Abnormal expression of cox-2, Fas, FasL, bcl-2, bax and NF-KB may involve in the inhibition of gastric carcinoma cells' apoptosis. Cox-2 upregulates the expression of bcl-2 and downregulates the expression of Fas and bax which inhibit the apoptosis of gastric carcinoma cells. Both NF-KB and cox-2 are highly expressed in gastric carcinoma tissues and NF-KB may upregulated the expression of cox-2.4. cox-2 may prompt the proliferation of SGC-7901 and inhibit their apoptosis through enhancing the synthesis of PGE3.