Inhibition of the metastatic spread and growth of B16-BL6 murine melanoma by a synthetic matrix metalloproteinase inhibitor

Int J Cancer. 1994 Aug 1;58(3):460-4. doi: 10.1002/ijc.2910580326.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / secondary
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / enzymology*
  • Melanoma, Experimental / secondary
  • Metalloendopeptidases / antagonists & inhibitors*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / blood
  • Phenylalanine / pharmacokinetics
  • Phenylalanine / pharmacology
  • Thiophenes / blood
  • Thiophenes / pharmacokinetics
  • Thiophenes / pharmacology*
  • Tissue Distribution

Substances

  • Thiophenes
  • Phenylalanine
  • batimastat
  • Metalloendopeptidases