TAXOL - A NOVEL RADIATION SENSITIZER
TAXOL - A NOVEL RADIATION SENSITIZER
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DOI：
10.1016/0360-3016(92)90888-o
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发表时间：
1992-01-01
影响因子：
7
通讯作者：
HALL, EJ
中科院分区：
文献类型：
--
作者：
TISHLER, RB;SCHIFF, PB;HALL, EJ
研究性抗肿瘤药物紫杉醇是一种来自紫杉（红豆杉属）的天然产物，目前正在一系列二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。紫杉醇是一种强效的微管稳定剂，它选择性地阻断细胞周期的G2期和M期的细胞，并且以时间 - 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。基于紫杉醇可作为一种细胞周期选择性放射增敏剂的原理，我们研究了药物 - 辐射联合暴露对人3级星形细胞瘤细胞系G18的影响。存活曲线分析表明，紫杉醇和电离辐射之间存在显著的相互作用，细胞杀伤增强的程度取决于紫杉醇浓度以及细胞周期中G2期或M期细胞的比例。在10%存活率时，10 nM紫杉醇的增敏比（SER）约为1.8。这些通过对循环充氧的放射抗性脑肿瘤细胞所获得的结果表明，在联合治疗方案中，适当的时间 - 浓度依赖的相互作用可能会带来显著的优势。
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.