Published online Jan 15, 2004. doi: 10.3748/wjg.v10.i2.172
Revised: August 20, 2003
Accepted: August 28, 2003
Published online: January 15, 2004
AIM: To determine the expression levels of three metabolic enzymes of fluoropyrimidines: thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in seven human gastrointestinal cancer cell lines, and to compare the enzyme levels with the sensitivity to 5-fluorouracil (5-FU) and 5-fluoro-2’-deoxyuridine (FdUrd).
METHODS: TS, TP and DPD mRNA levels were assessed by semi-quantitative RT-PCR, TP and DPD protein contents were measured by ELISA. Fifty percent inhibitory concentrations of growth (IC50), representing the sensitivity to drugs, were determined by MTT assay.
RESULTS: IC50 values ranged from 1.28 to 12.26 uM for 5-FU, and from 5.02 to 24.21 uM for FdUrd, respectively. Cell lines with lower DPD mRNA and protein levels tended to be more sensitive to 5-FU (P < 0.05), but neither TS nor TP correlated with 5-FU IC50 (P > 0.05). Only TS mRNA level was sharply related with FdUrd sensitivity (P < 0.05), but TP and DPD were not (P > 0.05). A correlation was found between mRNA and protein levels of DPD (P < 0.05), but not TP (P < 0.05).
CONCLUSION: DPD and TS enzyme levels may be useful indicators in predicting the antitumor activity of 5-FU or FdUrd, respectively.