Correlation of thymidylate synthase,thymidine phosphorylase and dihydropyrimidine dehydrogenase with sensitivity of gastrointestinal cancer cells to 5-fluorouracil and 5-fluoro-2′-deoxyuridine

摘要

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 12.26μM for 5-FU,and from 5.02 to 24.21μM for FdUrd,respectively.Cell lines with lower DPD mRNA and protein levels tended to be more sensitive to 5-FU (P0.05).Only TS mRNA level was sharply related with FdUrd sensitivity (P0.05).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.