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Updated: Aug 9, 2026

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
09:03

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells

Published on: November 23, 2014

UFT and its metabolites inhibit cancer-induced angiogenesis. Via a VEGF-related pathway

Y Basaki1, K Aoyagi, L Chikahisa

  • 1Cancer Research Laboratory, Hanno Research Center, Taiho Pharmaceutical Co, Ltd., Saitama, Japan. basaki@taiho.co.jp

Oncology (Williston Park, N.Y.)
|December 1, 2000
PubMed

Insights

UFT treatment significantly prolonged survival in animals with renal carcinoma lung metastasis by inhibiting angiogenesis. Its metabolites, including 5-FU and GHB, interfere with vascular endothelial growth factor (VEGF) signaling, reducing tumor microvessel density.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Biology

Background:

  • Spontaneous lung metastasis of renal cell carcinoma (RENCA) poses a significant clinical challenge.
  • Anti-angiogenesis is a promising therapeutic strategy for metastatic cancers.
  • UFT is an oral anticancer drug with known components and metabolites.

Purpose of the Study:

  • To investigate the anti-angiogenic effects of UFT on renal carcinoma lung metastasis.
  • To identify the specific components and metabolites of UFT responsible for anti-angiogenic activity.
  • To elucidate the mechanism by which UFT inhibits angiogenesis.

Main Methods:

  • Treatment of tumor-bearing animals with UFT to assess survival and metastatic burden.
  • Dorsal air sac assay to directly visualize and quantify angiogenesis.
  • In vitro studies using endothelial cells to assess the effect of UFT and its metabolites on VEGF-dependent responses.

Main Results:

  • UFT treatment significantly prolonged survival and reduced lung metastasis in RENCA-bearing mice.
  • UFT dose-dependently inhibited tumor-induced angiogenesis, decreasing microvessel density in metastatic foci.
  • UFT metabolites, including 5-fluorouracil (5-FU) and gamma-hydroxybutyric acid (GHB), were identified as key mediators of anti-angiogenic activity.
  • UFT, 5-FU, and GHB inhibited VEGF-induced angiogenesis in vitro and in vivo.
  • These effects were observed across various cancer cell lines, including gastric, lung, and colon cancers.

Conclusions:

  • UFT exhibits significant anti-angiogenic activity against renal carcinoma lung metastasis.
  • The anti-angiogenic effect of UFT is mediated, at least in part, by its metabolites interfering with VEGF signaling pathways.
  • UFT represents a potential therapeutic agent for cancers characterized by excessive VEGF production and angiogenesis.

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