Effects of thymidine phosphorylase on tumor aggressiveness and 5-fluorouracil sensitivity in cholangiocarcinoma.
OBJECTIVE
To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA).


METHODS
A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines.


RESULTS
TP mRNA and protein expression were decreased by 87.1% + or - 0.49% and 72.5% + or - 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil.


CONCLUSIONS
Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy.
Thanasai
Jongkonnee
J
Department of Clinical Microbiology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
Limpaiboon
Temduang
T
Jearanaikoon
Patcharee
P
Sripa
Banchob
B
Pairojkul
Chawalit
C
Tantimavanich
Srisurang
S
Miwa
Masanao
M
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D001650:Bile Duct Neoplasms / Q000188:drug therapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000473:pathology; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D034741:RNA, Small Interfering / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D034741:RNA, Small Interfering; D013939:Thymidine Phosphorylase; D005472:Fluorouracil