Inhibition of lymph node metastasis by an anti-angiogenic agent, TNP-470.
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.
Ohta
Y
Y
Department of Surgery I, School of Medicine, Kanazawa University, Japan.
Watanabe
Y
Y
Tabata
T
T
Oda
M
M
Hayashi
Y
Y
Endo
Y
Y
Tanaka
M
M
Sasaki
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology*; D003510:Cyclohexanes; D004354:Drug Screening Assays, Antitumor; D005260:Female; D008207:Lymphatic Metastasis / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D016133:Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000009:adverse effects / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol