Journal
WORLD JOURNAL OF GASTROENTEROLOGY
Volume 16, Issue 13, Pages 1631-1638Publisher
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v16.i13.1631
Keywords
Liver fluke; Cholangiocarcinoma; Thymidine phosphorylase; 5-fluorouracil; siRNA; Tumor aggressiveness; Cell migration
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Funding
- Thailand Research Fund [PHD/0037/2544]
- Centre for Research and Development of Medical Diagnostic Laboratories
- Faculty of Associated Medical Sciences, Khon Kaen University, Thailand
- Ministry of Education, Sports, Science, Culture and Technology, Japan
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AIM: 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% +/- 0.49% and 72.5% +/- 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. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy. (C) 2010 Baishideng. All rights reserved.
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