Platelet-derived growth factor A-chain synthetic peptide inhibits human glioma xenograft proliferation in nude mice.
The expression of polypeptide growth factors and their receptors by certain malignant human cell lines and the ability to grow these tumors as xenografts in murine hosts provides a useful setting to investigate the efficacy of antitumor agents. Exon 6 of the platelet-derived growth factor A-chain predicts a highly basic region consisting of 18 amino acids. Previously, we demonstrated that a synthetic peptide bearing this sequence interacts with a large population of binding sites at the cell surface and inhibits the binding and mitogenesis stimulated by several polypeptide growth factors (Khachigian et al J Biol Chem 267: 1660-1666, 1992; Khachigian and Chesterman, J Biol Chem 267: 7478-7482, 1992). In this report, we show that the exon 6 peptide can inhibit the mitogenic response of cultured human U-118 malignant glioma cells to normal human serum. When these cells are grown as subcutaneous xenografts in athymic nude mice, repeated intratumoral administration of the peptide results in dose-dependent growth inhibition. Indeed, injection of 0.48 mg of peptide five times a week abrogated growth during the entire course of treatment. Mouse weight or behavior did not differ significantly between control and treatment groups. Moreover, histologic examination of the tumors following treatment did not indicate necrosis. Thus, the exon 6 peptide can inhibit glioma cell proliferation both in culture and in an animal model without apparent side effects.
Khachigian
L M
LM
University of New South Wales Centre for Thrombosis and Vascular Research, Prince of Wales Hospital, Sydney, Australia.
Field
S L
SL
Crouch
R
R
Chesterman
C N
CN
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005091:Exons; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000637:transplantation
D010446:Peptide Fragments; D010982:Platelet-Derived Growth Factor