Influence of celecoxib, a selective COX-2 inhibitor, on the expressions of COX-2, VEGF, MMP-2 and MVD in Lewis lung carcinoma tissue

Objective To investigate the effects of celecoxib on transplanted Lewis lung carcinoma and the expressions of COX-2, VEGF, microvessel density (MVD) and MMP-2 in tumor tissue. Methods C57BL/6 mice were randomizedly divided into treatment group and control group, respectively. One day after inoculation of Lewis lung carcinoma cell suspension, treatment group began receiving 1000ppm celecoxib in the diet for 24 days. All mice were sacrificed on the 24th day after tumor implantation. The expressions of COX-2, VEGF, MMP-2 and MVD in xenografted tumor tissue were analyzed with immunohistochemical staining. Meanwhile, the expression of VEGF and MMP-2 mRNA was detected by RT-PCR. Results Celecoxib inhibited the growth of transplanted Lewis lung carcinoma significantly,with the inhibitory rate of 60. 1 %. The expression of COX-2 in the xenografted tumor tissue was higher in celecoxib-treated mice than in controls. However, there was no significant difference(P 0. 05). The VEGF staining score of tumor tissue in treatment group and control group were 2. 00±0. 82 and 2. 90±0. 88( P 0. 05) .respectively. The average MVD in two groups were 16. 70±7. 77 and 23. 15±4. 58( P 0. 05) .separately. Meanwhile,MMP-2 expression in xenografted tumor tissue determined by immunohlstochemical staining and RT-PCR was not significantly down-regulated after treatment with celecoxib. Conclusion Celecoxib has inhibitory effects on Lewis lung carcinoma. The activity of COX-2, which is inhibited by celecoxib,is probably related to the production of angiogenic factors such as VEGF modulated by COX-2. Antiangiogenesis may be another mechanism by which celecoxib exerts its chemopreventive and treatment effects.