Treatment of murine angiosarcoma with etoposide, TNP-470 and prednisolone.
To develop effective therapies for angiosarcoma, we investigated the anti-tumor effects of etoposide (ETO), TNP-470 and prednisolone (PSL) using an established murine angiosarcoma cell line (ISOS-1). We examined the direct anti-tumor and anti-angiogenic effects of these drugs on ISOS-1 cells and normal murine microvascular endothelial cells (mECs) in vitro. Cell growth of ISOS-1 was inhibited significantly by ETO, moderately by TNP-470, and not at all by PSL (IC(50): 0.25 microg/ml, 10 microg/ml, >8000 microg/ml, respectively). One the other hand, cell growth of mECs was inhibited significantly by TNP-470, slightly by PSL, and negligibly by ETO (IC(50): 0.85 ng/ml, 0.7 microg/ml, 10 microg/ml, respectively). In an in vivo assay, tumor growth of ISOS-1 was significantly inhibited by more than 2.5 mg/kg of ETO dose-dependently, and by more than 30 mg/kg of TNP-470, and 100 mg/kg of PSL individually. Combination treatments of ETO+TNP-470 and TNP-470+PSL showed synergistic enhancement of inhibition (% control inhibition: ETO vs. TNP-470 vs. ETO+TNP-470: 55 versus 55 vs. 16%) (% control inhibition: TNP-470 vs. PSL vs. TNP-470+PSL: 41 vs. 86 vs. 21%). ETO+PSL combination treatment, however, failed to show significant enhancement of anti-tumor effects. In conclusion, our results indicated that TNP-470 may be a very effective drug for angiosarcoma treatment, especially in combination with ETO or PSL. We eagerly anticipate the use of TNP-470 in clinical treatment of angiosarcoma.
Ma
G
G
Department of Dermatology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, 228-8555, Kanagawa, Japan.
Masuzawa
M
M
Hamada
Y
Y
Haraguchi
F
F
Tamauchi
H
H
Sakurai
Y
Y
Fujimura
T
T
Katsuoka
K
K
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D003510:Cyclohexanes; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005047:Etoposide / Q000627:therapeutic use*; D006394:Hemangiosarcoma / Q000188:drug therapy* / Q000473:pathology; D020128:Inhibitory Concentration 50; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011239:Prednisolone / Q000627:therapeutic use*; D012016:Reference Values; D012717:Sesquiterpenes / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D005047:Etoposide; D011239:Prednisolone; D000077609:O-(Chloroacetylcarbamoyl)fumagillol