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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Authors | Kinya Shinoda, Masahiko Shibuya, Suguru Hibino, Yasushi Ono, Kuniko Matsuda, Akira Takemura, Datong Zou, Yutaka Kokubo, Akiko Takechi, Shoji Kudoh |
Journal | International journal of oncology
(Int J Oncol)
Vol. 22
Issue 2
Pg. 281-8
(Feb 2003)
ISSN: 1019-6439 [Print] Greece |
PMID | 12527923
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiogenesis Inhibitors
- Antineoplastic Agents
- FYK 1388
- Guanidines
- Hydroxamic Acids
- Matrix Metalloproteinase Inhibitors
- Neoplasm Proteins
- Protease Inhibitors
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Topics |
- Angiogenesis Inhibitors
(pharmacology, therapeutic use)
- Animals
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Female
- Fibrosarcoma
(blood supply, drug therapy, enzymology, pathology, prevention & control, secondary)
- Guanidines
(chemistry, pharmacology, therapeutic use)
- Humans
- Hydroxamic Acids
(chemistry, pharmacology, therapeutic use)
- Injections, Subcutaneous
- Lung Neoplasms
(prevention & control, secondary)
- Matrix Metalloproteinase Inhibitors
- Mice
- Mice, Inbred BALB C
- Mice, Inbred ICR
- Mice, Nude
- Molecular Structure
- Neoplasm Proteins
(antagonists & inhibitors)
- Protease Inhibitors
(pharmacology, therapeutic use)
- Tumor Cells, Cultured
(drug effects)
- Xenograft Model Antitumor Assays
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