Inhibitory effect of cyclooxygenase-2 inhibitor on the metastasis of gastrointestinal tumor.

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Background. This study was designed to investigate the role of cyclooxygenase-2 (COX-2) in the liver metastasis and the effect of COX-2 inhibitor on metastasis of gastrointestinal tumor.Methods. Human colon cancer TK-4 was implanted subcutaneously (SC), peritoneally (PI) or orthotopically (on the surface of the cecum ; CI). The animals were sacrified 8 weeks after implantation and growing tumors were removed and examined. COX-1, -2 and VEGF mRNA level were determined by Northem Blotting analysis, and microvessel density (MVD) and apoptotic index were also examined. In addition, clinicopathological analysis was performed in 76 patients with colorectal cancer to clarify the role of COX-2 in the metastasis.Results. Liver metastasis developed most frequently in CI groups and the apoptotic index assessed by TUNEL staining was lowest in the CI group among the three groups. High expression of COX-2 had no connection with the density of ER-MP12-positive tumor microvesseles. Thirty-nine (51%) patients with colorectal cancer showed COX-2 over-expression, in whom liver metastasis developed more frequently than in those without overexpression (p<0.05). However, there was no significant difference in histological types, lymph node metastasis and peritoneal dissemination.Conclusions. These results suggest that COX-2 plays an important role in liver metastasis, and that high COX-2 expression may impair induction of apoptosis, but may not induce angiogenesis in colon cancer. COX-2 is one of target molecules for prevention of liver metastasis.