Anti-tumor angiogenic effect of a matrix metalloproteinase inhibitor MMI270.
We investigated the anti-angiogenic effects of a matrix metalloproteinase inhibitor, (MMI), so called MMI270, against B16-BL6 melanoma through the inhibition of the migrating and invasive abilities of hepatic sinusoidal endothelial (HSE) cells, as well as the formation of tube-like structures by HSE cells. MMI270, at the concentration of 12.5 micrograms/ml, significantly inhibited the migration and invasion of HSE cells, in addition to tube formation by approximately 40%. Furthermore, the enzymatic degradation of metalloproteinases MMP-9 and MMP-2 produced by HSE cells was inhibited by treatment with 1 microgram/ml of MMI270, showing 30% and 100% of inhibition in comparison to the control, respectively. The intraperitoneal administration of MMI270 (200 mg/kg, twice daily for 8 days) after the implantation of B16-BL6 melanoma cells into mice reduced the number of vessels towards the established primary tumor on the dorsal side of mice. These results suggest that MMI270 might be useful as an anti-tumor angiogenic drug.
Nakamura
Eliane Shizuka
ES
Department of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Koizumi
Keiichi
K
Yamaura
Takeshi
T
Saiki
Ikuo
I
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006877:Hydroxamic Acids; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011480:Protease Inhibitors / Q000494:pharmacology*; D011719:Pyrazines; D013449:Sulfonamides
D020533:Angiogenesis Inhibitors; C097658:CGS 27023A; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011719:Pyrazines; D013449:Sulfonamides; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9