Gastric Cancer
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 15, 2004; 10(2): 172-176
Published online Jan 15, 2004. doi: 10.3748/wjg.v10.i2.172
Correlation of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase with sensitivity of gastrointestinal cancer cells to 5-fluorouracil and 5-fluoro-2’-deoxyuridine
Tao Ma, Zheng-Gang Zhu, Yu-Bao Ji, Yi Zhang, Ying-Yan Yu, Bing-Ya Liu, Hao-Ran Yin, Yan-Zhen Lin
Tao Ma, Zheng-Gang Zhu, Yu-Bao Ji, Yi Zhang, Ying-Yan Yu, Bing-Ya Liu, Hao-Ran Yin, Yan-Zhen Lin, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Zheng-Gang Zhu, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China. digsurg@online.sh.cn
Telephone: +86-21-64373909 Fax: +86-21-64373909
Received: August 6, 2003
Revised: August 20, 2003
Accepted: August 28, 2003
Published online: January 15, 2004
Abstract

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.

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