TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis

Kyoko Yorozuya, Tetsuro Kubota, Masahiko Watanabe, Hirotoshi Hasegawa, Soji Ozawa, Masaki Kitajima, Lumi Muramatsu Chikahisa, Yuji Yamada

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

A number of receptor tyrosine kinases (RTKs) are involved in angiogenesis. TSU-68 (SU-6668) was developed as an inhibitor of RTKs involved in VEGF, bFGF and PDGF signaling, which then inhibits endothelial cell proliferation. We investigated the antitumor effects of TSU-68 against human colon cancer xenografts in male SCID mice and its anti-angiogenic activity using a dorsal air-sac (DAS) assay. TSU-68 was administered orally at a dose of 200 mg/kg twice daily. Mice bearing human colon carcinoma, HT-29, or WiDr xenografts were treated for 16 days. To determine the effect on hepatic metastasis, cell suspensions of HT-29 or WAV-I were injected into the spleen of mice on day 0, and mice treated for 28 days starting from day 1. For the DAS assay, HT-29, WiDr or WAV-I cells suspended in PBS at 2×107 cells/Millipore chamber were implanted subcutaneously into SCID mice, which were then treated from day 0 to 5, On day 6, the anti-angiogenic effects were assessed. Results indicated that TSU-68 significantly inhibited the growth of subcutaneous tumors. In the hepatic metastasis model, liver weights of the TSU-68-treated group were significantly reduced, compared to those of control mice. In the DAS assay, the angiogenic indices of the treated groups were significantly decreased for HT-29, WiDr and WAV-I tumors, with T/C ratios of 13.4, 50 and 35.3%, respectively. As TSU-68 significantly inhibited tumor growth and liver metastasis formation of human colon cancer xenografts, probably through anti-angiogenic activity, this agent may be useful for the treatment of colon cancer.

Original languageEnglish
Pages (from-to)677-682
Number of pages6
JournalOncology reports
Volume14
Issue number3
Publication statusPublished - 2005 Sep 1

Keywords

  • Anti-angiogenesis
  • Dorsal air-sac
  • Human colon cancer xenografts
  • SCID mouse
  • TSU-68

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis'. Together they form a unique fingerprint.

  • Cite this

    Yorozuya, K., Kubota, T., Watanabe, M., Hasegawa, H., Ozawa, S., Kitajima, M., Chikahisa, L. M., & Yamada, Y. (2005). TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis. Oncology reports, 14(3), 677-682.