The mechanism of growth-regulation of glioma cells by trapidil.
Trapidil is a PDGF antagonist that can inhibit the proliferation of the PDGF-producing glioma cells, U251MG. As the mechanism of growth-regulation by trapidil remains unclear, we studied its effect on the growth of U251MG cells. We performed a cell cycle analysis and examined the intracellular transduction pathway and oncogene expression in serum-stimulated glioma cells with or without trapidil. After the serum starvation for 3 days, glioma cell proliferation was stimulated by the addition of serum. Cell cycle analysis showed that cell cycle perturbations induced by trapidil included a decreased transition rate from G0-G1 to S phase, suggesting that some metabolic event is required for progress through the G0-G1 phase and that this event is sensitive to trapidil. Internal signal transduction mechanisms are central in the molecular control of cell growth. One such regulator is the protein kinase C(PKC) system and the c-fos gene is likely to be a direct target of intracellular signal transduction pathways. Therefore, we hypothesize that the intracellular PKC activity and c-fos expression of the trapidil-treated cells are suppressed. We posit that trapidil affects the intracellular signal transduction pathway PKC activity and c-fos expression in cells stimulated with serum containing growth factors.
Kuratsu
J
J
Department of Neurosurgery, Kumamoto University Medical School, Japan.
Sato
K
K
Saitoh
Y
Y
Takeshima
H
H
Morioka
M
M
Ushio
Y
Y
D015152:Blotting, Northern; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016762:Genes, fos; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D009693:Nucleic Acid Hybridization; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014192:Trapidil / Q000494:pharmacology*
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011493:Protein Kinase C; D014192:Trapidil