Dihydropyrimidine Dehydrogenase Activity and Messenger RNA Level May Be Related to the Antitumor Effect of 5-Fluorouracil on Human Tumor Xenografts in Nude Mice

摘要: We investigated the correlation between tumor sensitivity to 5-fluorouracil (5-FU) and enzymatic activity mRNA levels of thymidylate synthetase (TS) dihydropyrimidine dehydrogenase (DPD) using human xenografts in nude mice. Three gastric carcinoma (SC-1-NU, St-4, H-111), two colon (Co-4 Col-3-JCK), one pancreatic xenograft (PAN-3-JCK), breast (MX-1) were inoculated into When resultant tumors reached 100–300 mg, 5-FU was administered i.p. at a dose 60 mg/kg schedule three times every 4 days, antitumor evaluated as relative mean weight treated mice compared control Xenografts also untreated weighed 200–300 tissues resected for measurement tumoral TS DPD. DPD activities detected by TS-binding assay radioenzymatic assay, respectively. measured semiquantitative reverse transcription-PCR, with glyceraldehyde-3-phosphate coamplified an internal standard. ranged from 84.7 775.5 fmol/mg protein not detectable 79.7 pmol/min/mg protein, 0.51 9.90 0.93, The correlated observed levels. significantly sensitivity, high level resulting low 5-FU. In contrast, no observed. Tumoral may be useful indicators predicting