Relationship between expression of 5-fluorouracil metabolic enzymes and 5-fluorouracil sensitivity in esophageal carcinoma cell lines.
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 micromol/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.
Ando
T
T
Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan.
Ishiguro
H
H
Kuwabara
Y
Y
Kimura
M
M
Mitsui
A
A
Sugito
N
N
Mori
R
R
Ogawa
R
R
Katada
T
T
Fujii
Y
Y
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009962:Orotate Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013939:Thymidine Phosphorylase / Q000235:genetics / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D013939:Thymidine Phosphorylase; D005472:Fluorouracil