Characterization of 5-fluorouracil-resistant cholangiocarcinoma cell lines.
BACKGROUND
Although 5-fluorouracil (5-FU) is the drug of choice for the palliative treatment of cholangiocarcinoma (CCA), resistance to the drug is a therapeutic obstacle. The aim of this study was to explore the mechanisms underlying 5-FU resistance of CCA using cell lines derived from CCA associated with liver fluke infection.


METHODS
A stepwise exposure was used for inducing 5-FU-resistant CCA cell lines, and the expression of nine genes associated with 5-FU resistance was analyzed using real-time (RT)-PCR.


RESULTS
Altered expression of several genes involved in 5-FU resistance in CCA cell lines was observed. The expression levels of almost all target genes investigated including TP, DPD, ENT1, UNG1, TOP2A, BIRC5, TP73 and DeltaNp73 appeared to be significantly altered in these resistant strains. The expression of the TS gene tended to be increased but the fold change was not significantly different from their parental cell lines. UNG1 (a DNA repairing enzyme) and BIRC5 (an apoptotic inhibitor) expressions were increased whereas TP73 (a proapoptotic factor) expression levels decreased concomitantly.


CONCLUSIONS
Our study showed that increases in UNG1 and BIRC5 expression and concomitant decreases in TP73 expression may be associated with development of acquired 5-FU resistance in CCA lines and their phenotypes.
Namwat
Nisana
N
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. nisana@kku.ac.th
Amimanan
Piyawan
P
Loilome
Watcharin
W
Jearanaikoon
Patcharee
P
Sripa
Banchob
B
Bhudhisawasdi
Vajarabhongsa
V
Tassaneeyakul
Wichittra
W
D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; D005472:Fluorouracil