Prevention of liver metastasis of human colon cancer by selective matrix metalloproteinase inhibitor MMI-166.

Abstract

MMI-166 is a selective inhibitor of matrix metalloproteinase (MMP)-2 and MMP-9. Mice implanted a human colon cancer orthotopically received 200 mg/kg of MMI-166 orally for 5 weeks. Gelatin zymography demonstrated that the administration of MMI-166 remarkably decreased the active MMP-2 expression. Histological examination revealed that MMI-166 showed prominent effect on reduction of the invasive feature of the cancer cells and showed inhibitory effect on tumor vasculature, resulting in the significant decrease of microvessel density of the implanted tumor and liver metastasis compared with the control group. Conclusively, MMI-166 is a potent antiangiogenic oral agent for a human colon cancer.

• Authors: Kouji Oba, Hiroyuki Konno, Tatsuo Tanaka, Megumi Baba, Kinji Kamiya, Manabu Ohta, Takeshi Kaneko, Tsuyoshi Shouji, Akira Igarashi, Satoshi Nakamura
• Journal: Cancer letters (Cancer Lett) Vol. 175 Issue 1 Pg. 45-51 (Jan 10 2002) ISSN: 0304-3835 [Print] Ireland
• PMID: 11734335 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Matrix Metalloproteinase Inhibitors
• N-alpha-(4-(2-phenyl-2H- tetrazole-5-yl) phenyl sulfonyl)-D-tryptophan
• Sulfonamides

Topics

• Animals
• Body Weight (drug effects)
• Colonic Neoplasms (pathology)
• Enzyme Inhibitors (therapeutic use)
• Humans
• Liver Neoplasms (pathology, prevention & control, secondary)
• Matrix Metalloproteinase Inhibitors
• Mice
• Mice, Nude
• Organ Size (drug effects)
• Spleen (anatomy & histology)
• Sulfonamides (therapeutic use)
• Transplantation, Heterologous