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

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Jongkonnee Thanasai1, Temduang Limpaiboon, Patcharee Jearanaikoon

  • 1Department of Clinical Microbiology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.

World Journal of Gastroenterology
|April 1, 2010
PubMed
Abstract

Insights

Thymidine phosphorylase (TP) inhibition in cholangiocarcinoma cells reduced growth and migration. However, this may decrease effectiveness of 5-fluorouracil chemotherapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • Cholangiocarcinoma is an aggressive cancer with limited treatment options.
  • Thymidine phosphorylase (TP) is implicated in tumor growth and angiogenesis.
  • Understanding TP's role is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the function of thymidine phosphorylase (TP) in cholangiocarcinoma.
  • To evaluate the effects of TP inhibition using small interfering RNA (siRNA).

Main Methods:

  • Utilized a human cholangiocarcinoma cell line (KKU-M139) with high endogenous TP expression.
  • Transiently knocked down TP expression using siRNA.
  • Assayed cell growth, migration, angiogenesis, apoptosis, and chemosensitivity.

Main Results:

  • TP mRNA and protein levels were significantly reduced by siRNA.
  • TP inhibition decreased cholangiocarcinoma cell migration and angiogenesis.
  • TP knockdown reduced resistance to hypoxia-induced apoptosis and altered 5-fluorouracil sensitivity.

Conclusions:

  • Inhibiting TP may hinder angiogenesis-dependent cholangiocarcinoma growth and migration.
  • TP suppression might reduce the efficacy of 5-fluorouracil chemotherapy.

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