title: Effects of thymidine phosphorylase on tumor aggressiveness and 5-fluorouracil sensitivity in cholangiocarcinoma.
abstract: 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.
authors.affiliation: Department of Clinical Microbiology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Jongkonnee
authors.initials: J
authors.lastname: Thanasai
authors.forename: Temduang
authors.initials: T
authors.lastname: Limpaiboon
authors.forename: Patcharee
authors.initials: P
authors.lastname: Jearanaikoon
authors.forename: Banchob
authors.initials: B
authors.lastname: Sripa
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.forename: Srisurang
authors.initials: S
authors.lastname: Tantimavanich
authors.forename: Masanao
authors.initials: M
authors.lastname: Miwa
mesh_terms: 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*
chemical_list: D000964:Antimetabolites, Antineoplastic; D034741:RNA, Small Interfering; D013939:Thymidine Phosphorylase; D005472:Fluorouracil