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

  • Authors:
    • Kyoko Yorozuya
    • Tetsuro Kubota
    • Masahiko Watanabe
    • Hirotoshi Hasegawa
    • Soji Ozawa
    • Masaki Kitajima
    • Lumi Muramatsu Chikahisa
    • Yuji Yamada
  • View Affiliations

  • Published online on: September 1, 2005     https://doi.org/10.3892/or.14.3.677
  • Pages: 677-682
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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 2x107 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.

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September 2005
Volume 14 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yorozuya K, Kubota T, Watanabe M, Hasegawa H, Ozawa S, Kitajima M, Chikahisa LM and Yamada Y: TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis. Oncol Rep 14: 677-682, 2005
APA
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, 677-682. https://doi.org/10.3892/or.14.3.677
MLA
Yorozuya, K., Kubota, T., Watanabe, M., Hasegawa, H., Ozawa, S., Kitajima, M., Chikahisa, L. M., Yamada, Y."TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis". Oncology Reports 14.3 (2005): 677-682.
Chicago
Yorozuya, K., Kubota, T., Watanabe, M., Hasegawa, H., Ozawa, S., Kitajima, M., Chikahisa, L. M., Yamada, Y."TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis". Oncology Reports 14, no. 3 (2005): 677-682. https://doi.org/10.3892/or.14.3.677