Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) induce the proliferation of glioma cells
in vitro. Trapidil and suramin inhibit this growth factor-stimulated glioma cell growth, but the mechanisms are not fully understood. The effects of trapidil and suramin on PDGF and EGFinduced early biochemical events in T98G cells were studied. PDGF induced a rapid increase of intracellular free calcium concentration ([Ca
2+]i) in fura-2/acetoxymethyl ester-loaded single glioma (T98G) cells. This increase was completely inhibited by removal of extracellular Ca
2+ with ethylene glycol bis(β-aminoethyl ether)-N, N, N, N-tetraacetic acid but not by an L-type calcium channel blocker (nicardipine), suggesting that PDGF may cause calcium influx through voltage-independent calcium channels in T98G cells. Trapidil and suramin blocked the PDGF-induced calcium response and inhibited the PDGF-initiated tyrosine phosphorylation of the PDGF receptor as detected by Western blot analysis using an antibody specific for phosphotyrosine. Trapidil and suramin also inhibited EGF-initiated calcium response in T98G cells, but only partially inhibited EGF-initiated tyrosine phosphorylation at the same concentrations. Our results suggest that trapidil and suramin inhibit PDGF and EGF-initiated early biochemical events, and thus suppress growth factor-induced cell proliferation.
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