Suppression of rhabdomyosarcoma growth by fumagillin analog TNP-470.
The purpose of our study was to investigate a novel therapeutic approach for rhabdomyosarcoma (RMS) in an animal model. The pursuit of new therapeutic modalities for RMS is critically important since this type of tumor is the most common soft tissue sarcoma in children and because patients with metastatic disease may not be cured with current therapeutic modalities. We studied whether RMS growth may be suppressed by TNP-470, an analog of fumagillin, which was found to inhibit neoangiogenesis. Our data had shown that animals treated with TNP-470 (60 mg/kg), over a specific period of time, had approximately 50% smaller tumors than controls. Consistent with previous observations, treatment with TNP-470 decreases the level of the cyclin D1. Tumors dissected from TNP-470-treated animals had also considerable necrotic areas. In addition, TNP-470 had a direct cytotoxic effect on RMS cells in vitro. Our study has shown, therefore, that RMS in an animal model and in vitro responds to treatment with TNP-470, which suggests that the inhibitors of angiogenesis may be useful in a novel therapeutic design for RMS.
Kalebic
T
T
Molecular Oncology Section, Pediatric Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Tsokos
M
M
Helman
L J
LJ
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D003510:Cyclohexanes; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000473:pathology; D012717:Sesquiterpenes / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol