Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Radiat Oncol. 2012 Jan 27;7:9. doi: 10.1186/1748-717X-7-9.
To evaluate the cytotoxic effect of carbon ion radiotherapy and chemotherapy in glioblastoma cells in vitro.
The human glioblastoma (GBM) cell line U87 was irradiated with photon radiotherapy (RT) doses of 2 Gy, 4 Gy and 6 Gy. Likewise, irradiation with carbon ions was performed with single carbon doses of 0.125, 0.5, 2 and 3 Gy. Four chemotherapeutic substances, camptothecin, gemcitabine, paclitaxel and cisplatinum, were used for single and combination experiments. The assessment of the effect of single and double treatment on cell viability was performed using the clonogenic growth assay representing the radiobiological gold standard.
The RBE of carbon ions ranges between 3.3 and 3.9 depending on survival level and dose. All chemotherapeutic substances showed a clear does-response relationhips. in their characteristic concentrations. For subsequent combination experiments, two dose levels leading to low and medium reduction of cell survival were chosen. Combination experiments showed additive effects independently of the drugs' mechanisms of action. Paclitaxel and campthothecin demonstrated the most prominent cytotoxic effect in combination with carbon ion radiotherapy.
In conclusion, combination of carbon ion radiotherapy with chemotherapies of different mechanisms of action demonstrates additive effects. The most dominant effect was produced by paclitaxel, followed by camptothecin, as espected from previously published work. The present data serve as an important radiobiological basis for further combination experiments, as well as clinical studies on combination treatments.
评估碳离子放射治疗和化疗对体外脑胶质瘤细胞的细胞毒性作用。
采用光子放射治疗(RT)剂量 2 Gy、4 Gy 和 6 Gy 对人胶质母细胞瘤(GBM)细胞系 U87 进行照射。同样,采用单碳剂量 0.125、0.5、2 和 3 Gy 进行碳离子照射。使用喜树碱、吉西他滨、紫杉醇和顺铂 4 种化疗药物进行单药和联合实验。采用集落形成生长试验评估单药和双药治疗对细胞活力的影响,该试验是放射生物学的金标准。
碳离子的 RBE 取决于生存水平和剂量,范围在 3.3 到 3.9 之间。所有化疗药物在其特征浓度下均表现出明显的剂量-反应关系。对于后续的联合实验,选择了导致细胞存活率低和中度降低的两个剂量水平。组合实验显示出独立于药物作用机制的相加效应。紫杉醇和喜树碱与碳离子放射治疗联合显示出最显著的细胞毒性作用。
总之,碳离子放射治疗与不同作用机制的化疗联合具有相加作用。如先前发表的工作所预期的那样,紫杉醇产生的效果最显著,其次是喜树碱。这些数据为进一步的联合实验以及联合治疗的临床研究提供了重要的放射生物学基础。