Todo T, Adams E F, Fahlbusch R
Department of Neurosurgery, University of Erlangen-Nürnberg, Germany.
J Neurosurg. 1993 Mar;78(3):463-9. doi: 10.3171/jns.1993.78.3.0463.
In a previous study, the authors demonstrated that meningioma cells secrete platelet-derived growth factor (PDGF)-like molecules that stimulate their own growth in an autocrine manner. Based on that 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 meningiomas in culture. Trapidil showed a dose-dependent inhibition of meningioma cell proliferation in the absence of any exogenous mitogenic stimulation. The maximum effect was observed at a concentration of 100 micrograms/ml, with the decrease in cell growth ranging from 16% to 54% compared to control samples. Trapidil similarly inhibited the basal deoxyribonucleic acid (DNA) synthesis assessed by [3H]-thymidine incorporation in three of seven meningiomas. While the conditioned medium generated from meningioma cells remarkably stimulated the proliferation of meningioma cells (166% to 277% of control), this effect was strikingly inhibited by the addition of trapidil. Trapidil also inhibited conditioned medium-stimulated DNA synthesis, even when there was no effect on basal DNA synthesis. Furthermore, trapidil significantly inhibited the epidermal growth factor (EGF)-stimulated proliferation of meningioma cells. This inhibitory effect on EGF-stimulated cell proliferation was also observed in nontumorous fibroblasts, demonstrating that trapidil is not an antagonist specific to PDGF. The addition of trapidil (30 micrograms/ml) in combination with bromocriptine (1 microM) showed an additive inhibitory effect on the meningioma cell growth compared to trapidil or bromocriptine alone. The overall results suggest that trapidil exhibits an inhibitory effect on meningioma cell proliferation through 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 meningiomas.
在之前的一项研究中，作者证明脑膜瘤细胞分泌血小板源性生长因子（PDGF）样分子，这些分子以自分泌方式刺激其自身生长。基于这一发现，开展了一项研究，以检测曲匹地尔（一种已知对PDGF具有拮抗作用的药物）对培养的人脑膜瘤细胞增殖的影响。在没有任何外源性促有丝分裂刺激的情况下，曲匹地尔对脑膜瘤细胞增殖呈现剂量依赖性抑制作用。在浓度为100微克/毫升时观察到最大效应，与对照样品相比，细胞生长减少幅度为16%至54%。曲匹地尔同样抑制了通过[3H] - 胸腺嘧啶核苷掺入评估的7例脑膜瘤中3例的基础脱氧核糖核酸（DNA）合成。虽然脑膜瘤细胞产生的条件培养基显著刺激了脑膜瘤细胞的增殖（为对照的166%至277%），但添加曲匹地尔可显著抑制这种效应。曲匹地尔还抑制了条件培养基刺激的DNA合成，即使对基础DNA合成没有影响。此外，曲匹地尔显著抑制表皮生长因子（EGF）刺激的脑膜瘤细胞增殖。在非肿瘤性成纤维细胞中也观察到了对EGF刺激的细胞增殖的这种抑制作用，表明曲匹地尔不是PDGF特异性拮抗剂。与单独使用曲匹地尔或溴隐亭相比，添加曲匹地尔（30微克/毫升）与溴隐亭（1微摩尔）联合使用对脑膜瘤细胞生长具有相加抑制作用。总体结果表明，曲匹地尔通过阻断自分泌或外源性生长因子诱导的促有丝分裂刺激，对脑膜瘤细胞增殖具有抑制作用，可能被视为脑膜瘤医学治疗的一种可能的新方法。
