Rutter Abigail V, Siddique Muhammad R, Filik Jacob, Sandt Christophe, Dumas Paul, Cinque Gianfelice, Sockalingum Ganesh D, Yang Ying, Sulé-Suso Josep
Institute for Science and Technology in Medicine, School of Medicine, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, ST4 7QB, United Kingdom.
Cytometry A. 2014 Aug;85(8):688-97. doi: 10.1002/cyto.a.22488. Epub 2014 May 20.
Over the last few years, significant scientific insight on the effects of chemotherapy drugs at cellular level using synchrotron-based FTIR (S-FTIR) microspectroscopy has been obtained. The work carried out so far has identified spectral differences in cancer cells before and after the addition of drugs. However, this had to account for the following issues. First, chemotherapy agents cause both chemical and morphological changes in cells, the latter being responsible for changes in the spectral profile not correlated with biochemical characteristics. Second, as the work has been carried out in mixed populations of cells (resistant and sensitive), it is important to distinguish the spectral differences which are due to sensitivity/resistance to those due to cell morphology and/or cell mixture. Here, we successfully cloned resistant and sensitive lung cancer cells to a chemotherapy drug. This allowed us to study a more uniform population and, more important, allowed us to study sensitive and resistant cells prior to the addition of the drug with S-FTIR microscopy. Principal component analysis (PCA) did not detect major differences in resistant cells prior to and after adding the drug. However, PCA separated sensitive cells prior to and after the addition of the drug. This would indicate that the spectral differences between cells prior to and after adding a drug might reside on those more or less sensitive cells that have been able to remain alive when they were collected to be studied with S-FTIR microspectroscopy. This is a proof of concept and a feasibility study showing a methodology that opens a new way to identify the effects of drugs on more homogeneous cell populations using vibrational spectroscopy.
在过去几年中，利用基于同步加速器的傅里叶变换红外（S-FTIR）显微光谱技术，在细胞水平上对化疗药物的作用有了重要的科学认识。到目前为止所开展的工作已经确定了添加药物前后癌细胞的光谱差异。然而，这必须考虑以下问题。首先，化疗药物会引起细胞的化学和形态变化，后者导致光谱特征的变化与生化特性无关。其次，由于这项工作是在混合细胞群体（耐药和敏感细胞）中进行的，区分因对药物敏感/耐药导致的光谱差异与因细胞形态和/或细胞混合导致的光谱差异很重要。在这里，我们成功地将肺癌细胞克隆为对一种化疗药物耐药和敏感的细胞。这使我们能够研究更均匀的细胞群体，更重要的是，使我们能够在添加药物之前，用S-FTIR显微镜研究敏感和耐药细胞。主成分分析（PCA）在添加药物前后未检测到耐药细胞的主要差异。然而，PCA区分了添加药物前后的敏感细胞。这表明添加药物前后细胞之间的光谱差异可能存在于那些在被收集用于S-FTIR显微光谱研究时能够存活下来的或多或少敏感的细胞中。这是一个概念验证和可行性研究，展示了一种利用振动光谱识别药物对更均匀细胞群体作用的新方法。
