The FTIR spectrum of prostate cancer cells allows the classification of anticancer drugs according to their mode of action
The FTIR spectrum of prostate cancer cells allows the classification of anticancer drugs according to their mode of action
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DOI：
10.1039/c0an00872a
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发表时间：
2011-01-01
期刊：
影响因子：
4.2
通讯作者：
Goormaghtigh, Erik
中科院分区：
文献类型：
--
作者：
Derenne, Allison;Gasper, Regis;Goormaghtigh, Erik
在临床上失败的抗癌药物的数量远远超过那些被认为有效的抗癌药物，这表明进入临床的药物分子的选择程序需要改进。传统上，新药是根据它们杀死癌细胞的潜力进行评估的。这种方法显然是不够的，需要具有新作用模式的分子。我们认为，细胞暴露在抗癌药物的红外光谱可以提供一个机会，以获得药物诱导的代谢变化的指纹。由于细胞的红外光谱产生了样本中存在的所有化学键的精确图像，不同的药物靶标可能会产生不同的红外指纹，这些指纹具有正在研究的治疗剂的“作用模式”的特征。反过来，药物引起的代谢紊乱应该像细菌性别、物种和菌株可以分类一样进行分类。在这里，我们研究了一种人前列腺癌PC-3细胞株，该细胞系暴露于7种描述良好的抗分裂药物。在第一步中，确定了IC50值。对于FTIR成像，将PC-3细胞暴露在每种药物的IC50浓度下48h，在8 cm(-1)的光谱分辨率下获得约100幅4096个红外光谱的图像。我们用学生t检验表明，被测试的不同分子引起了不同的红外光谱修正。此外，当分析光谱形状时，已知会引起类似类型代谢紊乱的药物似乎会聚集在一起。最后，有监督的统计方法可以建立一个有效的判别模型。当将判别模型应用于全红外图像时，通常获得了良好的分类，并且误分类的光谱通常属于少数特定的细胞。综上所述，FTIR可用于药物作用的分类。
The number of anticancer agents that fail in the clinic far outweighs those considered effective, suggesting that the selection procedure for progression of drug molecules into the clinic requires improvement. Traditionally, new drugs are evaluated for their potential to kill cancer cell lines. This approach is obviously not sufficient, and molecules with new modes of action are required. We suggest here that the infrared spectrum of cells exposed to anticancer drugs could offer an opportunity to obtain a fingerprint of the metabolic changes induced by the drugs. Because the infrared spectrum of cells yields a precise image of all the chemical bonds present in the sample, different drug targets are likely to yield different infrared fingerprints characteristic of the 'mode of action' of the therapeutic agent under investigation. In turn, drug-induced metabolic disorders should be amenable to classification in the same way that bacteria gender, species, and strains can be classified. We examined here a human prostate cancer PC-3 cell line exposed to 7 well described antimitotics. In a first step the IC50 values were determined. For FTIR imaging, PC-3 cells were exposed to the IC50 concentration of each drug for 48 h. About one hundred images of 4096 IR spectra at 8 cm(-1) spectral resolution were acquired. We show with a Student t-test that the different molecules tested induced different infrared spectral modifications. Furthermore, drugs known to induce similar types of metabolic disturbances appear to cluster when spectrum shapes are analyzed. Finally, supervised statistical methods allowed the building of an efficient and discriminant model. When the discriminant model was applied to a full infrared image a good sorting was generally obtained and misclassified spectra generally belonged to a small number of specific cells. Taken all together these data suggest that FTIR could be used for the classification of drug action.