Introduction Nonsteroidal anti-inXammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 (COX-2) overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory eVects of the COX-2 inhibitor celecoxib on the growth of colorectal cancer liver metastases in a syngeneic rat model, CC531. Materials and methods The eVects of celecoxib on cell viability in vitro were evaluated by treatment of CC531 tumor cell cultures with celecoxib. In vivo, Wag/Rij rats were inoculated with CC531 tumor cells at two sites in the liver and treated with celecoxib starting one week before, or directly after tumor inoculation. Control rats were inoculated without treatment. Three weeks after tumor inoculation rats were sacriWced. Tumor size, immune cell inWltration, caspase-3 activity, PGE 2 and celecoxib levels were determined.Results CC531 tumors did not show COX-2 expression. Tumor growth was signiWcantly inhibited by celecoxib treatment in a dose dependent manner. Immune cell inWltration was decreased after celecoxib treatment, indicating that the immune system was not involved in preventing tumor growth. Tumor caspase-3 levels were only signiWcantly increased if treatment was started before tumor inoculation. Celecoxib serum concentration starting at 0.84 g/ml signiWcantly inhibited the outgrowth of CC531 liver tumors. In contrast, in vitro concentrations of celecoxib of at least 12 g/ml were needed to aVect tumor cell viability. Conclusion These results suggest that the inhibitory eVects of celecoxib on tumor growth are not by direct cytotoxicity, but by creating an unfavorable environment for tumor growth.
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