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Inhibition of growth of human tumor cells in nude mice by a metalloproteinase inhibitor

✍ Scribed by Kyozo Naito; Nobuo Kanbayashi; Shigeru Nakajima; Takashi Murai; Kyoko Arakawa; Susumu Nishimura; Akira Okuyama

Publisher: John Wiley and Sons
Year: 1994
Tongue: French
Weight: 694 KB
Volume: 58
Category: Article
ISSN: 0020-7136
DOI: 10.1002/ijc.2910580518

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✦ Synopsis

The effects of a new metalloproteinase inhibitor, BE 16627B [L-N-(N-hydroxy-2-isobutylsuccinynamoyl)-se~l-L-valine, M W 375.21 isolated from microbial cultures, on human tumor cell growth in nude mice were investigated. BEl6627B inhibited metalloproteinases in enzyme assays, as well as gelatinolysis and collagenolysis in cell cultures. BE166278 at 100 pg/ml showed no apparent cytotoxicity to human tumor cells in culture and its LDSo in mice was more than 1,000 mg/kg (i.p.). The effects of BE I6627B on the in vivo growth of 2 human tumor cell lines were examined: HT I080 fibrosarcoma, which overproduces metalloproteinases, and HCTl I 6 colon carcinoma, which barely secretes metalloproteinases. When BE I66278 was administered to mice at 2 mg/mouse/day by an osmotic pump implanted S.C. for 3 weeks from I week after i.v. inoculation of HTI 080 cells, the number and size of nodules of HTI 080 cells on the lung surface were reduced to 24.3 and 46.4%. respectively, of those of controls, and the increase in lung weight due to tumor-cell growth was inhibited 85.5% without body-weight loss. Moreover, BE16627B inhibited 71.2Y0 of the growth of

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