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

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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

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Heterografts
Colonic Neoplasms
Air Sacs
Neoplasm Metastasis
Liver
Growth
Neoplasms
SCID Mice
Receptor Protein-Tyrosine Kinases
Vascular Endothelial Growth Factor A
orantinib
5-((1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-propanoic acid
Hepatocytes
Suspensions
Colon
Spleen
Endothelial Cells
Cell Proliferation
Carcinoma
Weights and Measures

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Yorozuya, K., Kubota, T., Watanabe, M., Hasegawa, H., Ozawa, S., Kitajima, 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.

TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis. / Yorozuya, Kyoko; Kubota, Tetsuro; Watanabe, Masahiko; Hasegawa, Hirotoshi; Ozawa, Soji; Kitajima, Masaki; Chikahisa, Lumi Muramatsu; Yamada, Yuji.

In: Oncology Reports, Vol. 14, No. 3, 09.2005, p. 677-682.

Research output: Contribution to journalArticle

Yorozuya, K, Kubota, T, Watanabe, M, Hasegawa, H, Ozawa, S, Kitajima, M, Chikahisa, LM & Yamada, Y 2005, 'TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis', Oncology Reports, vol. 14, no. 3, pp. 677-682.
Yorozuya K, Kubota T, Watanabe M, Hasegawa H, Ozawa S, Kitajima M et al. TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis. Oncology Reports. 2005 Sep;14(3):677-682.
Yorozuya, Kyoko ; Kubota, Tetsuro ; Watanabe, Masahiko ; Hasegawa, Hirotoshi ; Ozawa, Soji ; Kitajima, Masaki ; Chikahisa, Lumi Muramatsu ; Yamada, Yuji. / TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis. In: Oncology Reports. 2005 ; Vol. 14, No. 3. pp. 677-682.
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