Antiproliferative effect of trapidil on PDGF-associated growth of human glioma cell lines in vitro.
The effects of trapidil on platelet-derived growth factor (PDGF)-associated growth of glioblastoma cells were studied. The assessment using PDGF-dependent rat lung endothelium cells revealed secretion of a PDGF-like factor from SF-126 cell line but not from SF-188. Human recombinant PDGF stimulated proliferation of both these glioblastoma cell lines. The anti-PDGF monoclonal antibody inhibited the growth of SF-126 more than SF-188. The results suggest the presence of an autocrine growth mechanism in SF-126 cells mediated by PDGF. The growth of both SF-126 and SF-188 cells was suppressed by trapidil, a specific PDGF antagonist, at 10 and 50 micrograms/ml, respectively. The proliferative response to exogenous PDGF and the antagonistic effect of trapidil were greater in the SF-126 cell line. In addition, trapidil markedly reduced production of prostaglandin E2 in both glioblastoma cell lines. This anti-proliferative effect on malignant glioma cells suggests that trapidil might be a new therapeutic agent for malignant gliomas.
Tada
M
M
Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo.
Aida
T
T
Hosokawa
M
M
Kobayashi
H
H
Sawamura
Y
Y
Abe
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001681:Biological Assay; D001932:Brain Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D004847:Epithelial Cells; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000502:physiology; D014192:Trapidil / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014192:Trapidil; D015232:Dinoprostone