Tishler R B, Schiff P B, Geard C R, Hall E J
Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, NY.
Int J Radiat Oncol Biol Phys. 1992;22(3):613-7. doi: 10.1016/0360-3016(92)90888-o.
The investigational antineoplastic agent, taxol, a natural product from the yew, Taxus sp. L., is currently being evaluated in a series of Phase II clinical trials. To date, the drug has shown activity against ovarian cancer, lung cancer, and melanoma. Taxol is a potent microtubule stabilizing agent that selectively blocks cells in the G2 and M phases of the cell cycle and is cytotoxic in a time-concentration dependent manner. It is well known from radiobiological principles that G2 and M are the most radiosensitive phases of the cell cycle. On the rationale that taxol could function as a cell-cycle selective radiosensitizer, we examined the consequences of combined drug-radiation exposures on the human grade 3 astrocytoma cell line, G18. Survival curve analysis shows a dramatic interaction between taxol and ionizing radiation with the degree of enhanced cell killing dependent on taxol concentration and on the fraction of cells in the G2 or M phases of the cell cycle. The sensitizer enhancement ratio (SER) for 10 nM taxol at 10% survival is approximately 1.8. These results obtained with cycling aerated radioresistant brain tumor cells indicate that significant advantage may derive from appropriate time-concentration dependent interactions in combined modality protocols.
研究性抗肿瘤药物紫杉醇是从红豆杉属植物中提取的一种天然产物，目前正在一系列II期临床试验中进行评估。到目前为止，该药物已显示出对卵巢癌、肺癌和黑色素瘤的活性。紫杉醇是一种有效的微管稳定剂，可选择性地阻断细胞周期的G2期和M期，并以时间-浓度依赖的方式具有细胞毒性。从放射生物学原理可知，G2期和M期是细胞周期中对辐射最敏感的阶段。基于紫杉醇可作为细胞周期选择性放射增敏剂的理论，我们研究了联合药物-辐射暴露对人3级星形细胞瘤细胞系G18的影响。存活曲线分析显示紫杉醇与电离辐射之间存在显著相互作用，增强的细胞杀伤程度取决于紫杉醇浓度以及细胞周期G2期或M期的细胞比例。在10%存活率时，10 nM紫杉醇的增敏增强比（SER）约为1.8。这些在增殖的耐辐射脑肿瘤细胞中获得的结果表明，在联合治疗方案中，适当的时间-浓度依赖相互作用可能会带来显著优势。
