The Effect of COX-2 Inhibitor on the Growth and Metastasis of Gastric Cancer Xenograft

ABSTRACT

PURPOSE: Tumor invasion and metastasis are known to be extremely important factors in the prognosis of cancer patients. Although recent studies have demonstrated that cyclooxygenase-2 (COX-2) is overexpressed in various cancers including gastric cancer, the mechanisms underlying the contribution of COX-2 to tumorigenesis and tumor promotion remain unclear. METHODS: In order to determine the role of COX-2 in tumor growth and metastasis, we investigated COX-2 expression, apoptosis and the expression of E-cadherin, CD44v6, MMP-2 and TIMP-2 in gastric cancer xenografts treated with meloxicam (a selective COX-2 inhibitor). RESULTS: Cells from the MKN45 gastric cancer cell line that overexpress COX-2 were inoculated subcutaneously into athymic mice. Oral administration with meloxicam reduced the tumor volume (P<0.01), induced apoptosis of cancer cells (P<0.01), suppressed the proliferation rates (P<0.01), increased the expression of E-cadhrin (P<0.05) and reduced the expression of MMP-2 and TIMP-2. CONCLUSION: The above data showed that COX-2 inhibitors can inhibit tumor growth and suppress metastatic potential by expression of adhesion molecules and suppression of metalloproteinases, suggesting that this inhibitor can be used as an additive anti-cancer drug in cases of stomach cancer with radical resection, although further evaluation is required.