RRC ID 17698
Author Sato J, Kimura T, Saito T, Anazawa T, Kenjo A, Sato Y, Tsuchiya T, Gotoh M.
Title Gene expression analysis for predicting gemcitabine resistance in human cholangiocarcinoma.
Journal J Hepatobiliary Pancreat Sci
Abstract BACKGROUND:Gemcitabine is a promising drug for cholangiocarcinoma treatment. However, the kinetics and metabolism of this drug in cholangiocarcinoma treatment are not well defined. We aimed to investigate the potential clinical role of gemcitabine metabolism-related genes in the gemcitabine sensitivity of cholangiocarcinoma and identify and characterize novel gemcitabine resistance-related genes.
METHODS:Expressions of genes related to gemcitabine sensitivity and gemcitabine metabolism were measured in 10 cholangiocarcinoma cell lines, and the association between gene expression and gemcitabine sensitivity was evaluated. Furthermore, gemcitabine-resistant cell lines were established from YSCCC cells and subjected to genome-wide microarray analysis. The 2-fold upregulated and downregulated genes were then subjected to pathway analysis.
RESULTS:p53R2 mRNA expression was significantly higher in gemcitabine-resistant cell lines (IC(50) > 1000 nM), and all subunits of ribonucleotide reductase were upregulated in the established gemcitabine-resistant cell lines. Microarray analysis revealed that the upregulated genes in the resistant cells belonged to the glutathione and pyrimidine metabolism pathways, and that the downregulated genes belonged to the N-glycan biosynthesis pathway.
CONCLUSIONS:Increased expression of p53R2 may predict gemcitabine resistance, and upregulated RNR activity may influence gemcitabine resistance in cholangiocarcinoma cells. Glutathione pathway-related genes were induced by continuous exposure to gemcitabine and may contribute to gemcitabine resistance.
Volume 18(5)
Pages 700-11
Published 2011-9
DOI 10.1007/s00534-011-0376-7
PMID 21451941
MeSH Bile Duct Neoplasms / drug therapy* Bile Duct Neoplasms / genetics Bile Duct Neoplasms / metabolism Bile Ducts, Intrahepatic* Cell Cycle Proteins / biosynthesis Cell Cycle Proteins / genetics* Cell Line, Tumor Cholangiocarcinoma / drug therapy* Cholangiocarcinoma / genetics Cholangiocarcinoma / metabolism DNA Repair Deoxycytidine / analogs & derivatives* Deoxycytidine / pharmacology Drug Resistance, Neoplasm / genetics* Gene Expression Regulation, Neoplastic* Humans Immunosuppressive Agents / pharmacology RNA, Neoplasm / genetics Real-Time Polymerase Chain Reaction Ribonucleotide Reductases / biosynthesis Ribonucleotide Reductases / genetics*
IF 2.877
Times Cited 19
Human and Animal Cells YSCCC (RCB1549) TKKK (RCB1907) TGBC1TKB (RCB1129) TGBC2TKB (RCB1130) TGBC14TKB (RCB1186) TGBC24TKB (RCB1196)