Treatment of murine angiosarcoma with etoposide, TNP-470 and prednisolone

To develop effective therapies for angiosarcoma, we investigated the anti-t umor effects of etoposide (ETO), TNP-470 and prednisolone (PSL) using an es tablished murine angiosarcoma cell line (ISOS-1). We examined the direct an ti-tumor and anti-angiogenic effects of these drugs on ISOS-1 cells and nor mal murine microvascular endothelial cells (mECs) in vitro. Cell growth of ISOS-1 was inhibited significantly by ETO, moderately by TNP-470, and not a t all by PSL (IC50: 0.25 mug/ml, 10 mug/ml, > 8000 mug/ml, respectively). O ne the other hand, cell growth of mECs was inhibited significantly by TNP-4 70, slightly by PSL, and negligibly by ETO (IC50: 0.85 ng/ml, 0.7 mug/ml, 1 0 mug/ml, respectively). In an in vivo assay, tumor growth of ISOS-1 was si gnificantly inhibited by more than 2.5 mg/kg of ETO dose-dependently, and b y more than 30 mg/kg of TNP-470, and 100 mg/kg of PSL individually. Combina tion treatments of ETO + TNP-470 and TNP-470 + PSL showed synergistic enhan cement of inhibition (% control inhibition: ETO vs. TNP-470 vs. ETO + TNP-4 70: 55 versus 55 vs. 16%) (%o control inhibition: TNP-470 vs. PSL vs. TNP-4 70 + PSL: 41 vs. 86 vs. 21%). ETO + PSL combination treatment, however, fai led to show significant enhancement of anti-tumor effects. In conclusion, o ur results indicated that TNP-470 may be a very effective drug for angiosar coma treatment, especially in combination with ETO or PSL. We eagerly antic ipate the use of TNP-470 in clinical treatment of angiosarcoma. (C) 2000 El sevier Science Ireland Ltd. All rights reserved.