Abstract |
Matrix metalloproteinases ( MMPs) have been implicated in tumor invasion, metastasis, and angiogenesis. We have recently shown that MMI-166, a new orally active MMP inhibitor specific for MMP-2 and -9, suppressed experimental metastasis of Lewis lung cancer, C-H1 human colon cancer, and pancreatic cancer without affecting tumor growth in vitro. In the present study, we determined whether oral administration of MMI-166 reduces tumor growth not only in such tumors but also in squamous cell carcinoma of head and neck (SCCHN). MMI-166 inhibited both activity of MMP-2 and -9 without affecting steady state levels of their mRNAs in SCCHN. Interestingly, protein levels of MMP-2 and -9 from the cultures were drastically diminished by culturing with MMI-166. This was also observed in xenografts of MMI-166-administered mice. In addition, daily oral administration of MMI-166 (100mg/kg) inhibited local tumor growth accompanied by the reduction of blood vessel density and Ki-67-positivity and increase in terminal deoxynucleotidyl transferase-mediated cUDP nick-end labeling (TUNEL)-positivity. These results suggested that orally administered MMI-166 reduced in vivo tumor growth of SCCHN through inhibition of angiogenesis and induction of apoptosis accompanied by the reduction of MMP productions and activities. Therefore, MMI-166 seems to be useful for tumor dormancy therapy of SCCHN.
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Authors | Hideaki Katori, Yuh Baba, Yukari Imagawa, Goshi Nishimura, Yuumi Kagesato, Emi Takagi, Akiko Ishii, Shunsuke Yanoma, Ryuji Maekawa, Takayuki Yoshioka, Yoji Nagashima, Yasumasa Kato, Mamoru Tsukuda |
Journal | Cancer letters
(Cancer Lett)
Vol. 178
Issue 2
Pg. 151-9
(Apr 25 2002)
ISSN: 0304-3835 [Print] Ireland |
PMID | 11867199
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Matrix Metalloproteinase Inhibitors
- N-alpha-(4-(2-phenyl-2H- tetrazole-5-yl) phenyl sulfonyl)-D-tryptophan
- Sulfonamides
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Topics |
- Animals
- Carcinoma, Squamous Cell
(blood supply, drug therapy, enzymology, pathology)
- Enzyme Inhibitors
(pharmacology, therapeutic use)
- Female
- Head and Neck Neoplasms
(blood supply, drug therapy, enzymology, pathology)
- Humans
- Matrix Metalloproteinase Inhibitors
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Neoplasm Transplantation
- Neovascularization, Pathologic
(drug therapy)
- Sulfonamides
(pharmacology, therapeutic use)
- Transplantation, Heterologous
- Tumor Cells, Cultured
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