Prevention of hepatic metastasis of human colon cancer by angiogenesis inhibitor TNP-470.
The antimetastatic effect of a potent angiogenesis inhibitor, O-(chloroacetyl-carbamoyl)fumagillol (TNP-470), was investigated in nude mice implanted with human colon cancer. Small pieces of tumors from three established human colon cancer cell lines (TK-3, TK-4, and TK-9), which were maintained in nude mice, were implanted into the cecal wall of nude mice via a small incision in the serosa. TNP-470 (20 or 30 mg/kg) was given s.c. every other day from day 10 after implantation, and the mice were sacrificed after 6 weeks. There was no difference in the weight of the implanted tumors (control group: 0.45 +/- 0.29 g versus treated group: 0.49 +/- 0.27 g). An antimetastatic effect of TNP-470 was clearly demonstrated in a dose-dependent manner. In the mice given 20 mg/kg TNP-470, liver metastasis developed in 3 of 10 cases. In the 30-mg/kg group, metastasis developed in only 1 of 17 mice, while it developed in 22 of 32 mice of the control group. The number of metastatic foci was significantly less in the treated groups. TNP-470 effectively prevented liver metastasis, however, but had no effect on the growth of the primary tumor. These results indicate that the angiogenesis inhibitor TNP-470 has a strong inhibitory activity against in vivo hepatic metastasis of human colon cancer.
Tanaka
T
T
Second Department of Surgery, Hamamatsu University School of Medicine, Japan.
Konno
H
H
Matsuda
I
I
Nakamura
S
S
Baba
S
S
D000230:Adenocarcinoma / Q000098:blood supply* / Q000188:drug therapy*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D003510:Cyclohexanes; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol