Differential cytostatic effect of sodium salicylate in human colorectal cancers using an individualized histoculture system

PURPOSE: Tumor metastasis is the major cause of colorectal cancer (CRC) mortality. Nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin have been shown to have an antineoplastic effect in CRC cell lines. Different patients, however, exhibit different chemosensitivity. In this study, we assessed the chemotherapeutic potential of sodium salicylate, an aspirin metabolite, by measuring its cytostatic effect in an individualized three-dimensional histoculture system. METHODS: Histocultured cancer tissues were treated with sodium salicylate at concentrations from 1 to 10 m M for 24 or 48 h. Inhibition of DNA synthesis was measured in terms of inhibition of bromodeoxyuridine (BrdU) incorporation.RESULTS: The concentration response of individual cancer tissues could be categorized into four groups ranging from the most to the least sensitive to sodium salicylate. Of 20 cancer tissues, 12 (60%) showed a concentration-effect relationship with sodium salicylate in the clinically relevant concentration range (IC50 1.2+/-0.4 to 3.8+/-0.5 m M). Doubling the exposure time decreased the IC50 in four specimens, suggesting that a similar inhibition might be achieved with a lower concentration over an extended time. None of the right-sided cancers was sensitive to sodium salicylate ( P=0.002). CONCLUSIONS: Sodium salicylate had a cytostatic effect on the majority of histocultured CRC tissues. The varying chemosensitivity of the cancers possibly reflected underlying differences, for example in relation to cancer site, thus emphasizing further the usefulness of this clinically relevant system in tailoring chemotherapy to the individual patient.