Comparison of the inhibitory effect of the angiogenesis inhibitor, TNP-470, and mitomycin C on the growth and liver metastasis of human colon cancer

Int J Cancer. 1995 Apr 10;61(2):268-71. doi: 10.1002/ijc.2910610221.


Angiogenesis inhibitors have attracted considerable interest. The anti-tumor and anti-metastatic effects of TNP-470, an angiogenesis inhibitor, and mitomycin C (MMC), a representative anti-neoplastic agent, were investigated using a xenotransplanted human colon cancer, TK-4. Suturing of small pieces of TK-4 tumors to the cecal wall in nude mice (orthotopic transplantation) induced liver metastasis. Mice were randomly divided into 3 groups; a control group given saline solution, a group receiving TNP-470 and a group receiving MMC. TNP-470 was given s.c. on alternate days for 5 weeks from day 10 after cecal transplantation and MMC was administered intraperitoneally (i.p.) once a week from day 10 after cecal transplantation. MMC significantly inhibited cecal tumor growth. In the control group, liver metastases developed in 9 out of 10 mice, including 3 with more than 20 metastatic foci. Liver metastasis also developed in 8 out of 10 mice receiving MMC, 2 of which had many metastases. In contrast, liver metastasis developed in only 2 out of 8 mice in the TNP-470 group and neither of these animals had numerous metastases.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / therapeutic use*
  • Body Weight / drug effects
  • Cell Division / drug effects
  • Colonic Neoplasms / blood supply*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / pathology*
  • Cyclohexanes
  • Humans
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / prevention & control*
  • Liver Neoplasms / secondary*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mitomycin / therapeutic use*
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / prevention & control*
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Sesquiterpenes / therapeutic use*


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