In vivo experiments were performed on breast cancer xenografts to examine whether the combination therapy with S-1, an oral dihydrouracil dehydrogenase (DPD) inhibitory fluoropyrimidine, plus docetaxel functions as an additive/synergistic modulator in tumor growth. The human breast cancer xenograft, MDA-MB-435SHM, was inoculated into SCID female mice. The tumor growth and thymidylate synthase (TS)/DPD activity of tumors treated with the agents were investigated. The T/C value (relative mean tumor weight of the treated group/relative tumor weight of the control group) of the group treated with docetaxel, S-1 and combination therapy were 45.3, 63.1 and 29.8%, respectively; suggesting the positive antitumor effects of the combination therapy in particular. In addition, significant down-regulation of DPD activity was also observed in the tumors treated with S-1, docetaxel and their combination. Down-regulation of the DPD activity of the tumors is also considered to be correlated with the antitumor effect of the treated groups, suggesting its influence on the synergistic effect of the combination therapy.

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