Angiogenesis inhibitor TNP-470 can suppress hepatocellular carcinoma growth without retarding liver regeneration after partial hepatectomy.
OBJECTIVE
We investigated the suppressive effect of the angiogenesis inhibitor TNP-470 on accelerated hepatocellular carcinoma (HCC) growth in the regenerating liver.


METHODS
After 70% partial hepatectomy (PH), AH-130 cells were injected into the portal vein of Donryu rats. A control group was given the vehicle only, and the treated group was given 10 mg/kg TNP-470 subcutaneously every second day, from 24 h after tumor implantation, seven times. On day 14, tumor growth was evaluated by the number of foci on the liver surface, liver weight, and the microvessel density of the tumor.


RESULTS
The number of foci was significantly less in the treated group (116.5 +/- 103.1) than in the control group (319.3 +/- 223.1) ( P < 0.05), as was microvessel density, which was 31.3 +/- 14.0/mm2 in the treated group and 61.2 +/- 18.9/mm2 in the control group ( P < 0.05). The liver tended to weigh less in the treated group (12.15 +/- 1.28 g) than in the control group (15.22 +/- 5.35 g). We also assessed whether TNP-470 retards liver regeneration. Seven days after 70% PH, the liver weight in the treated group was similar to that in the control group. Total bilirubin, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase were not higher in the treated group than in the control group.


CONCLUSIONS
TNP-470 can suppress HCC growth without retarding liver regeneration after PH.
Kinoshita
Shigeki
S
Department of Surgical Oncology and Thoracic Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Hirai
Ryuji
R
Yamano
Toshihisa
T
Yuasa
Ichiro
I
Tsukuda
Kazunori
K
Shimizu
Nobuyoshi
N
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000556:secondary / Q000601:surgery; D003510:Cyclohexanes; D006498:Hepatectomy; D008113:Liver Neoplasms / Q000098:blood supply* / Q000556:secondary / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol