Prevention of liver metastasis of human colon cancer by selective matrix metalloproteinase inhibitor MMI-166.
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.
Oba
Kouji
K
Department of Surgery II, Hamamatsu University School of Medicine, 1-20-1 Handayama, 431-3192, Hamamatsu, Japan.
Konno
Hiroyuki
H
Tanaka
Tatsuo
T
Baba
Megumi
M
Kamiya
Kinji
K
Ohta
Manabu
M
Kaneko
Takeshi
T
Shouji
Tsuyoshi
T
Igarashi
Akira
A
Nakamura
Satoshi
S
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary*; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008819:Mice, Nude; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000033:anatomy & histology; D013449:Sulfonamides / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; C419963:N-alpha-(4-(2-phenyl-2H- tetrazole-5-yl) phenyl sulfonyl)-D-tryptophan; D013449:Sulfonamides