Inhibition of lymph node metastasis by an anti-angiogenic agent, TNP-470

Br J Cancer. 1997;75(4):512-5. doi: 10.1038/bjc.1997.89.

Abstract

We assessed the inhibitory action of TNP-470 on lymph node metastasis in a metastatic model system using athymic nude mice. Mice were injected subcutaneously with 5 x 10(6) HT-1080 cells in the right groin. TNP-470 (10, 30 and 100 mg kg-1) was injected subcutaneously nine times in total every other day from the 7th day after tumour inoculation. Axillar and inguinal lymph nodes were dissected, and DNA was extracted 5 weeks after tumour inoculation. Specific detection of a human beta-globin-related sequence in metastasized human tumour cells in nude mice was done by the polymerase chain reaction (PCR) technique and analysed by Southern blotting. Anti-tumour effects on primary sites were seen only in the 100 mg kg-1 treatment group. Lymph node metastasis of transplanted HT-1080 cells was seen in all mice of the no treatment group (5/5). On the other hand, incidences of lymph node metastasis in treated mice were 2/4 mice (100 mg kg-1, 2/5 mice (30 mg kg-1) and 4/5 mice (10 mg kg-1). The inhibition ratios of lymph node metastasis were 82.3% at 10 mg kg-1, 97.2% at 30 mg kg-1 and 97.5% at 100 mg kg-1 respectively. This agent may be useful to inhibit lymph node metastasis.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / adverse effects
  • Antibiotics, Antineoplastic / pharmacology*
  • Cyclohexanes
  • Drug Screening Assays, Antitumor
  • Female
  • Lymphatic Metastasis / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Polymerase Chain Reaction
  • Sesquiterpenes / adverse effects
  • Sesquiterpenes / pharmacology*

Substances

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