Apoptosis as a predictor of paclitaxel-induced radiosensitization in human tumor cell lines.
Apoptosis as a predictor of paclitaxel-induced radiosensitization in human tumor cell lines.
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发表时间：
1999-09
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通讯作者：
Belma Kurdoglu;N. Cheong;J. Guan;Benjamin W. Corn;Walter John Curran;G. Iliakis
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作者：
Belma Kurdoglu;N. Cheong;J. Guan;Benjamin W. Corn;Walter John Curran;G. Iliakis
紫杉醇是一种对多种人类肿瘤具有抗肿瘤活性的萜类化合物。紫杉醇的细胞毒性被认为主要来源于微管的稳定化，这是由于微管蛋白聚合的增强导致细胞在细胞周期的有丝分裂（M）期积累。由于细胞周期的这一阶段中的细胞已知是放射敏感的，因此认为紫杉醇除了其直接毒性之外，还可以使肿瘤细胞群对放射敏感。评价紫杉醇在培养细胞中的放射增敏潜力的研究一直不明确，只有大约50%的测试细胞系显示放射增敏。为了解释这种变异性，我们提出了这样的假设，即紫杉醇放射增敏细胞的能力可能与其诱导细胞凋亡的效率呈负相关。为了验证这一假设，我们研究了紫杉醇诱导的细胞凋亡和放射增敏在7个人类肿瘤细胞系。这些细胞系中约有一半表现出与低凋亡指数相关的放射增敏作用（用10或20 nM紫杉醇处理48小时后<20%）。结果表明，紫杉醇治疗后，细胞凋亡的水平，可以预测紫杉醇诱导的放射增敏，它可以作为一个参数，优化联合治疗方案。
Paclitaxel is a deterpene with antitumor activity against a variety of human neoplasms. Paclitaxel cytotoxicity is thought to derive mainly from a stabilization of microtubules as a result of enhanced tubulin polymerization that leads to an accumulation of cells in the mitotic (M) phase of the cell cycle. Because cells in this phase of the cell cycle are known to be radiosensitive, it was thought that paclitaxel, in addition to its direct toxicity, may also sensitize tumor cell populations to radiation. Studies evaluating the radiosensitizing potential of paclitaxel in cultured cells have been equivocal, with only approximately 50% of the tested cell lines showing radiosensitization. To explain this variability, we advanced the hypothesis that the ability of paclitaxel to radiosensitize cells may be inversely correlated to the efficiency with which it induces apoptosis. To test this hypothesis, we studied paclitaxel-induced apoptosis and radiosensitization in seven human tumor cell lines. Approximately one-half of these cell lines showed radiosensitization that was associated with a low apoptotic index (<20% after a 48-h treatment with 10 or 20 nM paclitaxel). The results suggest that the level of apoptosis, after paclitaxel treatment, may predict for paclitaxel-induced radiosensitization, and that it could be introduced as a parameter for the optimization of combined treatment protocols.