Cordes N, Plasswilm L, Sauer R
Department of Radiation Oncology, University Hospital Erlangen-Nuernberg, Germany.
Strahlenther Onkol. 1999 Apr;175(4):175-81. doi: 10.1007/BF02742360.
Optimal dose and schedule of paclitaxel in combined drug-irradiation treatment could not be determined for most of tumors yet. The aim of this study was to compare in vitro cytotoxicity and radiosensitizing abilities as a function of single paclitaxel (Taxol) exposure in tumor and fibroblastic cells using different drug incubation irradiation intervals.
A lung-carcinoma (SK-LU-1), glioblastoma (U-138 MG) and rodent fibroblast cell line (HyB14FAF28) were used. The clonogenic assay was applied for survival investigation. alpha beta-values were calculated using the linear-quadratic model (log S = -alpha D - beta D2). Cytotoxicity of Taxol was examined at 0 to 50 microM. Combined Taxol-radiotherapy exposure was accomplished with 10 microM Taxol plus 10 Gy irradiation (RT) following after a 1-hour and 9-hour interval. For controls cells were exposed to Cremophor EL/ethanol (CEL/eth) and a phosphate buffered saline (PBS).
Single Taxol exposure (10 microM) resulted in 0.54/0.50/0.84 (3-hours incubation) and 0.094/0.48/0.82 (15-hours incubation) survival of SK-LU-1, U-138 MG and HyB14FAF28 cells, respectively. Taxol concentrations from 2 to 50 microM only had cytotoxic effect in tumor cells. Single dose RT (10 Gy) led to cell survival of 0.0006/0.006/0.03. The diluent CEL/eth also showed cytotoxic activity. Taxol plus RT led to cell survival of 0.00025/0.0014/0.042 (1 hour) and 0.0004/0.0019/0.04 (9 hours) without significant difference between chosen time intervals. alpha beta-values showed great variation lacking evidence for definite radiosensitization. alpha increase after Taxol and alpha decrease after CEL/eth exposure were detected.
The data presented demonstrate a potential beneficial effect, described as co-operation, by combining Taxol and RT in human tumor cells and rodent fibroblasts. High intrinsic alpha components of the tumor cells as well as CEL/eth's antagonizing actions could be likely to disturb and influence paclitaxel's abilities leading to radiosensitization.
对于大多数肿瘤而言，在联合药物 - 放射治疗中紫杉醇的最佳剂量和给药方案尚未确定。本研究的目的是使用不同的药物孵育 - 照射间隔，比较紫杉醇单次暴露对肿瘤细胞和成纤维细胞的体外细胞毒性和放射增敏能力。
使用肺癌细胞系（SK - LU - 1）、胶质母细胞瘤细胞系（U - 138 MG）和啮齿动物成纤维细胞系（HyB14FAF28）。采用克隆形成试验进行生存研究。使用线性二次模型（log S = -αD - βD²）计算αβ值。在0至50微摩尔浓度下检测紫杉醇的细胞毒性。紫杉醇与放疗联合暴露是在1小时和9小时间隔后，用10微摩尔紫杉醇加10 Gy照射（RT）完成的。对于对照组，细胞暴露于聚氧乙烯蓖麻油/乙醇（CEL/eth）和磷酸盐缓冲盐水（PBS）。
紫杉醇单次暴露（10微摩尔）导致SK - LU - 1、U - 138 MG和HyB14FAF28细胞的存活率分别为0.54/0.50/0.84（3小时孵育）和0.094/0.48/0.82（15小时孵育）。2至50微摩尔浓度的紫杉醇仅对肿瘤细胞有细胞毒性作用。单次剂量放疗（10 Gy）导致细胞存活率为0.0006/0.006/0.03。稀释剂CEL/eth也显示出细胞毒性活性。紫杉醇加放疗导致细胞存活率为0.00025/0.0014/0.042（1小时）和0.0004/0.0019/0.04（9小时），所选时间间隔之间无显著差异。αβ值显示出很大差异，缺乏明确放射增敏的证据。检测到紫杉醇处理后α增加，CEL/eth暴露后α降低。
所呈现的数据表明，在人肿瘤细胞和啮齿动物成纤维细胞中，联合使用紫杉醇和放疗具有潜在的有益效果，表现为协同作用。肿瘤细胞的高内在α成分以及CEL/eth的拮抗作用可能会干扰和影响紫杉醇导致放射增敏的能力。
