Cancer Therapy
Efficacy of the MMP inhibitor MMI270 against lung metastasis following removal of orthotopically transplanted human colon cancer in rat
Yutaka Ogata,
Keiko Matono,
Motowo Nakajima, Teruo Sasatomi,
Tomoaki Mizobe,
Hideaki Nagase,
Kazuo Shirouzu,
Corresponding Author
Yutaka Ogata
Department of Surgery, Kurume University School of Medicine, Japan
Fax: +81-942-34-0709
Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume City, Fukuoka 830-0011, JapanSearch for more papers by this authorKeiko Matono
Department of Surgery, Kurume University School of Medicine, Japan
Search for more papers by this authorTeruo Sasatomi
Department of Surgery, Kurume University School of Medicine, Japan
Search for more papers by this authorTomoaki Mizobe
Department of Surgery, Kurume University School of Medicine, Japan
Search for more papers by this authorHideaki Nagase
Kennedy Institute of Rheumatology Division, Imperial College London, United Kingdom
Search for more papers by this authorKazuo Shirouzu
Department of Surgery, Kurume University School of Medicine, Japan
Search for more papers by this authorYutaka Ogata,
Keiko Matono,
Motowo Nakajima, Teruo Sasatomi,
Tomoaki Mizobe,
Hideaki Nagase,
Kazuo Shirouzu,
Corresponding Author
Yutaka Ogata
Department of Surgery, Kurume University School of Medicine, Japan
Fax: +81-942-34-0709
Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume City, Fukuoka 830-0011, JapanSearch for more papers by this authorKeiko Matono
Department of Surgery, Kurume University School of Medicine, Japan
Search for more papers by this authorTeruo Sasatomi
Department of Surgery, Kurume University School of Medicine, Japan
Search for more papers by this authorTomoaki Mizobe
Department of Surgery, Kurume University School of Medicine, Japan
Search for more papers by this authorHideaki Nagase
Kennedy Institute of Rheumatology Division, Imperial College London, United Kingdom
Search for more papers by this authorKazuo Shirouzu
Department of Surgery, Kurume University School of Medicine, Japan
Search for more papers by this authorAbstract
We have investigated the antitumor effects of synthetic MMP inhibitor MMI270 against postoperative lung metastasis from colon cancer in nude rat. The KM12SM human colon cancer cells were injected into the cecal wall, and at 5 weeks after the injection, the cecum was removed including the tumor. Then, 30 mg/kg of MMI270 was administered perorally twice per day for 2 or 4 weeks, either immediately after removal or after week 2 after the removal. At week 7 after the removal, lung metastasis was significantly inhibited by the early administration of MMI270 immediately after the tumor removal but not by the late administration. The survival rates were significantly higher in the rats treated by early administration of MMI270 compared to the survival rate in untreated rats. Moreover, no lung metastasis was detected in some rats with 24-weeks' survival treated by early administration. Lower microvessel density, lower PCNA Index and higher Apoptotic Index in the lung metastases of the rats treated with MMI270 were found compared to those in untreated rats. A beneficial effect of by early administration of MMI270 against postoperative lung metastases may be expected through inhibiting neovascularization of metastases in nude rat. © 2005 Wiley-Liss, Inc.
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