Université de Sherbrooke, Sherbrooke, Canada.
J Neurooncol. 2010 Apr;97(2):187-93. doi: 10.1007/s11060-009-0011-5. Epub 2009 Sep 17.
Despite significant advances, the radiotherapy and chemotherapy protocols marginally improve the overall survival of patients with glioblastoma. Lipoplatin(TM), and Lipoxal(TM), the liposomal formulations of cisplatin and oxaliplatin respectively, were tested on the F98 glioma cells for their ability to improve the cell uptake and increase the synergic effect when combined with ionizing radiation. The cytotoxicity and synergic effect of platinum compounds were assessed by colony formation assay, while the cellular uptake was measured by Inductively Coupled Plasma Mass Spectrometer (ICP-MS). After 4 h exposure with platinum compounds, cells were irradiated (1.5-6.6 Gy) with a (60)Co source. The liposomal formulations were compared to their liposome-free analogs and to carboplatin. The concomitant treatment of F98 cells with carboplatin and radiation produced the highest radiosensitizing effect (30-fold increase). Among the platinum compounds tested, Lipoplatin(TM) produced the most promising results. This liposomal formulation of cisplatin improved the cell uptake by 3-fold, and its radiosensitizing potential was enhanced by 14-fold. Although Lipoxal(TM) can potentially reduce the adverse effect of oxaliplatin, a synergic effect with radiation was measured only when incubated at a concentration higher than its IC50. Conversely, concomitant treatment with cisplatin did not result in a synergic effect, as in fact a radioprotective effect was measured on the F98 cells. In conclusion, among the five platinum compounds tested, carboplatin and Lipoplatin(TM) showed the best radiosensitizing effect. Lipoplatin(TM) seems the most promising since it led to the best cellular incorporation and has already been reported to be less neurotoxic than other platinum compounds.
尽管取得了重大进展，但放射治疗和化学疗法方案仅略微改善了胶质母细胞瘤患者的总生存率。顺铂和奥沙利铂的脂质体制剂 Lipoplatin（TM）和 Lipoxal（TM）分别在 F98 神经胶质瘤细胞上进行了测试，以评估其提高细胞摄取能力并与电离辐射联合使用时增加协同作用的能力。通过集落形成测定评估铂化合物的细胞毒性和协同作用，而通过电感耦合等离子体质谱仪（ICP-MS）测量细胞摄取。铂化合物暴露 4 小时后，用（60）Co 源照射细胞（1.5-6.6 Gy）。将脂质体制剂与无脂质体的类似物和卡铂进行比较。F98 细胞同时接受卡铂和辐射治疗产生了最高的放射增敏作用（增加了 30 倍）。在所测试的铂化合物中，Lipoplatin（TM）产生了最有希望的结果。这种顺铂的脂质体制剂将细胞摄取提高了 3 倍，其放射增敏潜力提高了 14 倍。尽管 Lipoxal（TM）可以潜在地降低奥沙利铂的不良反应，但仅在孵育浓度高于其 IC50 时才测量到与辐射的协同作用。相反，同时使用顺铂不会产生协同作用，因为实际上在 F98 细胞上测量到了放射保护作用。总之，在所测试的五种铂化合物中，卡铂和 Lipoplatin（TM）显示出最佳的放射增敏作用。Lipoplatin（TM）似乎最有前途，因为它导致了最佳的细胞摄取，并且已经报道其神经毒性比其他铂化合物小。
