Inhibition of the metastatic spread and growth of B16-BL6 murine melanoma by a synthetic matrix metalloproteinase inhibitor.
The synthetic matrix metalloproteinase inhibitor batimastat was tested for its ability to inhibit growth and metastatic spread of the B16-BL6 murine melanoma in syngeneic C57BL/6N mice. Intraperitoneal administration of batimastat resulted in a significant inhibition in the number of lung colonies produced by B16-BL6 cells injected i.v. The effect of batimastat on spontaneous metastases was examined in mice inoculated in the hind footpad with B16-BL6 melanoma. The primary tumor was removed surgically after 26-28 days. Batimastat was administered twice a day from day 14 to day 28 (pre-surgery) or from day 26 to day 44 (post-surgery). With both protocols, the median number of lung metastases was not significantly affected, but there was a significant reduction in the weight of the metastases. Finally, the effect of batimastat was examined on s.c. growth of B16-BL6 melanoma. Batimastat administered daily, starting at day of tumor transplantation, resulted in a significant growth delay, whereas treatment starting at advanced stage tumor only reduced tumor growth marginally. Our results indicate that a matrix metalloproteinase inhibitor can not only prevent the colonization of secondary organs by B16-BL6 cells but also limit the growth of solid tumors.
Chirivi
R G
RG
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Garofalo
A
A
Crimmin
M J
MJ
Bawden
L J
LJ
Stoppacciaro
A
A
Brown
P D
PD
Giavazzi
R
R
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000201:enzymology* / Q000556:secondary; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D013876:Thiophenes / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution
D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D008666:Metalloendopeptidases