Identification of genes associated with sensitivity to 5-fluorouracil and cisplatin in hepatoma cells.
BACKGROUND
The prognosis of patients with advanced hepatoma is grim. Although chemotherapy is adapted to such patients, the efficacy is low and the outcome cannot be predicted before therapy. In this study, we aimed to identify genes associated with sensitivity to 5-fluorouracil and cisplatin, drugs widely used in treatment, using gene expression profiles.


METHODS
Gene expression was evaluated in eight human hepatoma cell lines using an in-house cDNA microarray including 2300 known genes. The 50% growth inhibitory concentrations (GI50) of 5-fluorouracil and cisplatin were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and designated as chemosensitivity. Genes with expression ratios associated with GI50 were selected using the permutation test.


RESULTS
For 5-fluorouracil and cisplatin, 21 and 40 genes, respectively, were selected. From among the genes associated with 5-fluorouracil and cisplatin, several encoding metabolic enzymes were selected. In addition, several genes involved in the cell cycle and transcription were identified.


CONCLUSIONS
We identified genes that may be associated with sensitivity to 5-fluorouracil and cisplatin. A list of these genes may be useful to elucidate how these drugs work on human hepatoma.
Hoshida
Yujin
Y
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Moriyama
Masaru
M
Otsuka
Motoyuki
M
Kato
Naoya
N
Goto
Tadashi
T
Taniguchi
Hiroyoshi
H
Shiratori
Yasushi
Y
Seki
Naohiko
N
Omata
Masao
M
D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002945:Cisplatin; D005472:Fluorouracil