4.1 Article

Relationship between expression of 5-fluorouracil metabolic enzymes and 5-fluorouracil sensitivity in esophageal carcinoma cell lines

Journal

DISEASES OF THE ESOPHAGUS
Volume 21, Issue 1, Pages 15-20

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1111/j.1442-2050.2007.00700.x

Keywords

dihydropyrimidine dehydrogenase; esophageal squamous cell carcinoma; quantitative reverse transcriptase-polymerase chain reaction; thymidylate synthase

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5-Fluorouracil (5-FU) is a key drug in the treatment of esophageal squamous cell carcinoma (ESCC). Gene expression of 5-FU metabolic enzymes such as thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT), has recently been investigated in order to predict the 5-FU sensitivity of several cancers. We examined the relationship between such gene expression and 5-FU sensitivity in 25 ESCC cell lines. TS, DPD, TP and OPRT mRNA levels were assessed by real-time polymerase chain reaction. The 50% inhibitory concentrations (IC50) of 5-FU in 25 ESCC cell lines were determined by cell proliferation assay. IC50 values for 5-FU ranged from 1.00 to 39.81 mu mol/L. There were significant positive correlations between IC50 and TS mRNA expression (R-2 = 0.5781, P < 0.0001) and DPD mRNA expression (R-2 = 0.3573, P = 0.0016). There were no correlations between IC50 and TP or OPRT mRNA expression. TS and DPD mRNA expression levels may be useful indicators in predicting the anti-tumor activity of 5-FU in ESCC.

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