Antiproliferative effect of trapidil, a platelet-derived growth factor antagonist, on a glioma cell line in vitro.
Platelet-derived growth factor (PDGF) is produced by glioma cells. However, there is heterogeneity among glioma cell lines in the production of PDGF. It has been demonstrated that U251MG cells produce a PDGF-like molecule while U105MG cells do not. Trapidil, a specific antagonist of PDGF, competes for receptor binding with PDGF. Therefore, the inhibitory effect of trapidil on the proliferation of glioma cells was investigated in vitro using two glioma cell lines. At 100 micrograms/ml, trapidil significantly inhibited the proliferation of U251MG cells (which produce the PDGF-like molecule). At the same trapidil concentration, the proliferation of U105MG cells (which do not produce the PDGF-like molecule) was not inhibited. The inhibitory effect of trapidil was remarkable on Days 3 and 4 of culture. After 4 days of incubation, the proliferation of U251MG cells was 46% of the control preparation. Trapidil enhanced the antitumor effect of 3-[4-amino-2-methyl-5-pyrimidinyl)ethyl)-1-(2-chloroethyl)-1-nitrosourea (ACNU) against U251MG cells. The enhancing effect was highest on Days 4 and 6 of culture. After 6 days of incubation in the presence of 100 micrograms/ml trapidil and 1 microgram/ml ACNU, the proliferation of U251MG cells was 18% of the control preparation. These findings suggest that trapidil interrupts the autocrine loop at the PDGF and PDGF-receptor level and that combination therapy with trapidil and ACNU may be useful in the treatment of glioma.
Kuratsu
J
J
Department of Neurosurgery, Kumamoto University Medical School, Japan.
Ushio
Y
Y
D000818:Animals; D005910:Glioma / Q000473:pathology*; D015376:Nimustine / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology*; D013498:Suramin / Q000494:pharmacology; D013997:Time Factors; D014192:Trapidil / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D010982:Platelet-Derived Growth Factor; D011743:Pyrimidines; D015376:Nimustine; D013498:Suramin; D014192:Trapidil