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Department of Neurosurgery, International Medical Center Hospital, Tokyo, Japan Two human malignant glial cell lines, U-251 and NMCG-I were used in this study. NMCG-I cell lines were been established from an astrocytoma, grade III by our clinic. Glial cells secrete platelet-derived growth factor (PDGF) - like molecules that stimulate their own growth in an autocrine manner. Based on this finding, a study was undertaken to examine the effect of trapidil, a drug known to have an antagonistic action against PDGF, on cell proliferation of human glial cell lines. Trapidil showed dose-dependent inhibition of glial cell proliferation in the absence of any exogenous mitogenic stimulation. The maximum effect was observed at a concentration of 100 mg/ml, with the decrease in cell growth compared to control cell lines (55% decrease for NMCG-I and 47% decrease for U-251). While the conditioned medium generated from U-251 and NMCG-I cell lines remarkably stimulated the proliferation of glial cells, with an increase of 67% for the control U-251 cell lines and 140% for the control NMCG-I cell lines, this effect was strikingly inhibited by the addition of trapidil. Epidermal growth factor remarkably stimulated the proliferation of glial cells, with an increase of 50% for the control U-251 cell lines and 73% for the control NMCG-I cell lines and this effect was also strikingly inhibited by the addition of trapidil. The maximum inhibitory effect, with a trapidil dose of 100 mg/ml, showed a 30% and 50% decrease in cell number, for U-251 and NMCG-1 respectively, compared to the EGF-stimulated cell growth. The overall results suggest that trapidil exhibits an inhibitory effect on glial cell proliferation by blocking the mitogenic stimulation induced by autocrine or exogenous growth factors, and may be considered as a possible new approach to the medical treatment of glial tumors. Keywords : Glial cells, trapidil, platelet derived growth factor, autocrine system