Induction of Dihydropyrimidine Dehydrogenase Expression by Mitomycin C in Colorectal Cancer
Since thymidine phosphorylase (TP) is an essential enzyme for the activation of capecitabine to 5-fluorouracil (5-FU) in tumors, TP up-regulators should enhance the efficacy of capecitabine. Dihydropyrimidine dehydrogenase (DPD), on the other hand, is considered to be a key enzyme in the catabolism of 5-FU, and its high expression in a tumor is thought to reduce the efficacy of 5-FU against tumors. The aim of this study was to confirm whether or not mitomycin C (MMC) is a TP and/or DPD regulator. Biopsy specimens were obtained from 62 colorectal cancer patients preoperatively by colonoscopy. After a biopsy, 33 patients received neoadjuvant chemotherapy with MMC and underwent operations after 1-13 days. Using biopsy and operative specimens, TP and DPD levels in the tumors were examined. Patients were divided into three groups; an MMC(-) group (no MMC), a Short group (operation within four days after MMC) and a Long group (operation over six days after MMC). In the MMC(-) and Short groups, no significant differences in DPD levels before and after MMC were observed. In the Long group, on the other hand, DPD levels were elevated (p=0.026). As for TP, MMC did not raise the levels of TP in the MMC(-) and Short groups, but it tended to do so in the Long group (p=0.13). Although MMC appears to be a TP up-regulator, it is also a DPD up-regulator at appropriate intervals.