Cyclooxygenase-2,Cyclooxygenase-2 Specific Inhibitor And It's Relationship With The Expression Of CD44V6,MMP-9 In Gastric Cancer

Objective To study the expression of COX-2,CD44V6 and MMP-9 in humangastric cancer , And the effects of NS-398, a specfic cyclooxygenase-2 (COX-2)enzyme inhibitor on the cell growth and the mRNA expression of CD44V6 andMMP-9 in a gastric cancer cell line SGC7901.Methods Protein expression of COX-2,CD44V6 and MMP-9 in 73 cases ofhuman gastric cancer tissues were examined by immunohistochemical S-Pstaining method; The expression of CD44V6 and MMP-9 protein in the SGC7901gstric cancer cells were detected by immunohistochemical technique. The effectof NS398 on the inhibition of PGE₂ serection in SGC-7901 gastric cancer cellswere detected by ELISA; after 0,50umol/L,100umol/L and 200 umol/L NS-398treatment the cell growth were measured by MTT,The expression of CD44V6 andMMP-9 mRNA in the SGC7901 gastric cancer cells before and after NS-398treatment were detected by RT-PCR.Results Positive rates of COX-2,CD44V6,MMP-9 expression in gatriccancer were 58.8%(43/73),47.8%(35/73) and45.2%(33/73),the expression ofCOX-2 was significantly correlated with CD44V6 and MMP-9 expression(P<0.01).The positive rate of COX-2,CD44V6 or MMP-9 expression wassignificantly different in gastric cancer tissues with and without lymphametastasis.Significant difference was found in the expression of COX-2,CD44V6or MMP-9 between gastric cancer tissue with and without lympha metastasis(P<0.05).The expression of COX-2,CD44V6 and MMP-9 were correlated withlympha metastasis of gastric cancer. And Protein expression of COX-2,CD44V6and MMP-9 were found in SGC7901 cells. The PGE2 production wassignificantly inhibited by NS-398, while a 64.3% inhibition rate was achieved by200　mol/L NS-398 treament. The inhibition showed a time-andconcentration-dependence. 24h after NS-398 treatment, the mRNA expression ofCD44V6 and MMP-9 were downregulated. When the concentration of NS-398 at200mmol/L, the expression of CD44V6 and MMP-9 mRNA were inhibited to45.7% and 43.6% of control, respectively.Conclusion The overexpression of COX-2 was associated with thecarcinogenesis of gastric cancer. The invasion and metastasis of gastric cancermay be promoted by COX-2 through upregulating the expression of CD44V6 andMMP-9. NS-398 inhibited not only the cell growth and PGE2 production, but alsothe mRNA expression of CD44V6 and MMP-9, the metastasis related genes, inSGC7901 cells, which suggested a potential use of COX-2 specific inhibitor in thegastric caner therapy.