Antiproliferative effect of multiple autocrine loop blockade in human malignant glioma cell lines.
The effects of specific antibodies against growth factors and receptors on deoxyribonucleic acid (DNA) synthesis in two established human glioma cell lines, A172 and TM-1, were examined. Anti-platelet-derived growth factor (PDGF), anti-basic fibroblast growth factor (bFGF), and anti-epidermal growth factor receptor (EGF-R) antibodies inhibited thymidine incorporation by both cell lines in serum-free medium. Antibody specific to transforming growth factor-alpha only slightly suppressed DNA synthesis by both cell lines. Although the antiproliferative effects of anti-PDGF and anti-bFGF antibodies decreased in serum-supplemented medium, the effect of anti-EGF-R antibody was little changed. The combination of anti-PDGF, anti-bFGF, and anti-EGF-R antibodies significantly inhibited thymidine incorporation by the two cell lines even in serum-supplemented medium. This preliminary study suggests that simultaneous blockade of multiple autocrine loops may provide a new approach to the treatment of human malignant gliomas.
Department of Neurosurgery, Toyama Medical and Pharmaceutical University, Faculty of Medicine.
M
M
Kurimoto
K
K
Nogami
T
T
Ogiichi
M
M
Nishijima
A
A
Takaku
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005910:Glioma / Q000473:pathology*; D005956:Glucose-6-Phosphate Isomerase / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D010982:Platelet-Derived Growth Factor; D016211:Transforming Growth Factor alpha; D016222:Fibroblast Growth Factor 2; D011505:Protein-Tyrosine Kinases; D005956:Glucose-6-Phosphate Isomerase; D013936:Thymidine