The designed angiostatic peptide anginex synergistically improves chemotherapy and antiangiogenesis therapy with angiostatin.
Recently, we demonstrated that the designed peptide anginex displays potent antiangiogenic activity. The aim of the present study was to investigate anginex treatment as a single-agent therapy and to test its ability to improve conventional chemotherapy and antiangiogenesis therapy. In a human ovarian carcinoma mouse model, anginex inhibited tumor growth by 70%. When anginex was combined with a suboptimal dose of carboplatin, tumors regressed to an impalpable state. Anginex plus angiostatin worked synergistically to inhibit tumor growth. Assessment of microvessel density suggested that the antitumor activity of anginex is mediated by angiogenesis inhibition. In any of the experiments, no sign of anginex-induced toxicity was observed.
Dings
Ruud P M
RP
Departments of Biochemistry, University of Minnesota Health Sciences Center, Minneapolis, Minnesota 55455, USA. mayox001@tc.umn.edu
Yokoyama
Yumi
Y
Ramakrishnan
Sundaram
S
Griffioen
Arjan W
AW
Mayo
Kevin H
KH
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D043168:Angiostatins; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology*; D016190:Carboplatin / Q000008:administration & dosage; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage; D010455:Peptides; D010958:Plasminogen / Q000008:administration & dosage; D011506:Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; C111993:betapep-25 protein, synthetic; D043168:Angiostatins; D010958:Plasminogen; D016190:Carboplatin