Effects of thymidine phosphorylase on tumor aggressiveness and 5-fluorouracil sensitivity in cholangiocarcinoma.

Abstract

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% + 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.

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.

• Authors: Jongkonnee Thanasai, Temduang Limpaiboon, Patcharee Jearanaikoon, Banchob Sripa, Chawalit Pairojkul, Srisurang Tantimavanich, Masanao Miwa
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 16 Issue 13 Pg. 1631-8 (Apr 07 2010) ISSN: 2219-2840 [Electronic] United States
• PMID: 20355241 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• RNA, Small Interfering
• Thymidine Phosphorylase
• Fluorouracil

Topics

• Antimetabolites, Antineoplastic (pharmacology)
• Apoptosis
• Bile Duct Neoplasms (drug therapy)
• Carcinoma, Squamous Cell (drug therapy)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Cholangiocarcinoma (drug therapy)
• Endothelium, Vascular (pathology)
• Fluorouracil (therapeutic use)
• Humans
• Neoplasm Invasiveness
• Neovascularization, Pathologic
• RNA, Small Interfering (metabolism)
• Thymidine Phosphorylase (metabolism)