A novel matrix metalloproteinase inhibitor, FYK-1388 suppresses tumor growth, metastasis and angiogenesis by human fibrosarcoma cell line

  • Authors:
    • Kinya Shinoda
    • Masahiko Shibuya
    • Suguru Hibino
    • Yasushi Ono
    • Kuniko Matsuda
    • Akira Takemura
    • Datong Zou
    • Yutaka Kokubo
    • Akiko Takechi
    • Shoji Kudoh
  • View Affiliations

  • Published online on: February 1, 2003     https://doi.org/10.3892/ijo.22.2.281
  • Pages: 281-288
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Abstract

The matrix metalloproteinases (MMPs) are likely to contribute to tumor cell invasion, metastasis and angiogenesis. Several MMP inhibitors have been developed, recently and their anti-tumor efficacy is being evaluated in clinical trials. FYK-1388 is a novel broad MMP inhibitor which blocks the activity of MMP-1, -2, -3, -7, -9, -13 and -14 (MT-MMP-1). It is especially effective against MMP-2 and -9 more so than other MMP inhibitors such as Marimastat, Ro 32-3555 and D-2163. Here, we investigated the anti-tumor efficacy of FYK-1388 using the human fibrosarcoma cell line HT-1080. These cells produced MMP-2 and -9, which FYK-1388 inhibited at a dose of 10−8 M. FYK-1388 at 0.2 mg/mouse/day significantly suppressed tumor growth when given by s.c. injection for 22 days, experimental lung metastasis after 5 days s.c. injection and also suppressed tumor-induced angiogenesis in the dorsal air sac assay after 7 days s.c. injection. In the MTT assay, FYK-1388 had no effect on the in vitro growth of HT-1080 cells. These results suggest that FYK-1388 possesses anti-tumor efficacy as a result of inhibiting angiogenesis through the suppression of MMP-2 and -9 activity.

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February 2003
Volume 22 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Shinoda K, Shibuya M, Hibino S, Ono Y, Matsuda K, Takemura A, Zou D, Kokubo Y, Takechi A, Kudoh S, Kudoh S, et al: A novel matrix metalloproteinase inhibitor, FYK-1388 suppresses tumor growth, metastasis and angiogenesis by human fibrosarcoma cell line. Int J Oncol 22: 281-288, 2003
APA
Shinoda, K., Shibuya, M., Hibino, S., Ono, Y., Matsuda, K., Takemura, A. ... Kudoh, S. (2003). A novel matrix metalloproteinase inhibitor, FYK-1388 suppresses tumor growth, metastasis and angiogenesis by human fibrosarcoma cell line. International Journal of Oncology, 22, 281-288. https://doi.org/10.3892/ijo.22.2.281
MLA
Shinoda, K., Shibuya, M., Hibino, S., Ono, Y., Matsuda, K., Takemura, A., Zou, D., Kokubo, Y., Takechi, A., Kudoh, S."A novel matrix metalloproteinase inhibitor, FYK-1388 suppresses tumor growth, metastasis and angiogenesis by human fibrosarcoma cell line". International Journal of Oncology 22.2 (2003): 281-288.
Chicago
Shinoda, K., Shibuya, M., Hibino, S., Ono, Y., Matsuda, K., Takemura, A., Zou, D., Kokubo, Y., Takechi, A., Kudoh, S."A novel matrix metalloproteinase inhibitor, FYK-1388 suppresses tumor growth, metastasis and angiogenesis by human fibrosarcoma cell line". International Journal of Oncology 22, no. 2 (2003): 281-288. https://doi.org/10.3892/ijo.22.2.281