Suppression of pulmonary metastasis by angiogenesis inhibitor TNP-470 in murine osteosarcoma

Int J Cancer. 1995 Mar 29;61(1):148-52. doi: 10.1002/ijc.2910610125.


We treated a murine osteosarcoma cell line, LM8, which preferentially metastasizes to the lungs, with a new angiogenesis inhibitor, TNP-470, to evaluate the efficacy of this compound in the suppression of pulmonary metastasis of osteosarcoma. In an in vivo experiment, tumor cells were inoculated i.v. into C3H mice, and TNP-470 or vehicle alone (control group) was administered s.c. every day for 3 weeks. In the TNP-470-treated groups, both the number of pulmonary metastatic nodules and the lung wet weight were significantly reduced in a dose-dependent manner. Similarly, vascular density in the metastatic tumors estimated by immunohistochemical staining with anti-von-Willebrand factor antibody as an endothelial marker were significantly reduced. No severe side-effects were found. In an in vitro experiment, viable tumor cells were counted after 3 days' treatment with TNP-470. The 50% inhibitory concentration was 0.6 ng/ml for LM8, which was more sensitive than other tumor cells previously reported. Our results show that TNP-470 suppresses the pulmonary metastasis of LM8 and suggest that both its anti-angiogenic activity and cytostatic activity towards LM8 are responsible for the antitumor effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / therapeutic use*
  • Bone Neoplasms / blood supply*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / pathology*
  • Cell Division / drug effects
  • Cyclohexanes
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / prevention & control*
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Osteosarcoma / blood supply*
  • Osteosarcoma / drug therapy
  • Osteosarcoma / pathology*
  • Sesquiterpenes / therapeutic use*
  • Tumor Cells, Cultured / drug effects


  • Antibiotics, Antineoplastic
  • Cyclohexanes
  • Sesquiterpenes
  • O-(Chloroacetylcarbamoyl)fumagillol