Unité MéDIAN, Université de Reims Champagne-Ardenne, CNRS UMR 6237-MEDyC, UFR de Pharmacie, IFR53, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
Anal Bioanal Chem. 2009 Dec;395(7):2293-301. doi: 10.1007/s00216-009-3140-y. Epub 2009 Oct 2.
Identifying early cellular events in response to a chemotherapy drug treatment, in particular at low doses that will destroy the highest possible number of cancer cells, is an important issue in patient management. In this study, we employed Fourier transform infrared spectroscopy as a potential tool to access such information. We used as model the non-small cell lung cancer cell line, Calu-1. They were exposed to cytostatic doses (0.1 to 100 nM for 24, 48 and 72 h) of gemcitabine, an anti-tumour drug, currently used in treatment of lung cancer patients. In these conditions, inhibition of cell proliferation ranges from weak (< or = 5%), to moderate (approximately 23%), to high (82-95%) without affecting cell viability. Following drug treatment as a function of doses and incubation times, the spectra of cell populations and of individual cells were acquired using a bench-top IR source and a synchrotron infrared microscope. It is demonstrated that spectral cell response to gemcitabine is detectable at sublethal doses and that effects observed on cell populations are similar to those from single cells. Using cluster analysis, spectra could be classified in two main groups: a first group that contains spectra of cells exhibiting a weak or moderate proliferation rate and a second group with spectra from cells presenting a high growth inhibition. These results are promising since they show that effects of subtoxic doses can also be monitored at the single-cell level with the clinical implications that this may have in terms of patient benefit and response to chemotherapy.
确定化疗药物治疗的早期细胞事件，特别是在低剂量下，以尽可能多地杀死癌细胞，这是患者管理中的一个重要问题。在这项研究中，我们采用傅里叶变换红外光谱作为一种潜在的工具来获取这些信息。我们使用非小细胞肺癌细胞系 Calu-1 作为模型。它们暴露于细胞毒性剂量（0.1 至 100 nM，持续 24、48 和 72 小时）的吉西他滨中，吉西他滨是一种抗肿瘤药物，目前用于治疗肺癌患者。在这些条件下，细胞增殖的抑制范围从弱（<或=5%）到中度（约 23%）到高（82-95%），而不影响细胞活力。在药物处理的剂量和孵育时间的函数下，使用台式红外源和同步辐射红外显微镜获取细胞群体和单个细胞的光谱。结果表明，吉西他滨对亚致死剂量的细胞光谱反应是可检测的，并且在细胞群体中观察到的效应与单细胞中的效应相似。通过聚类分析，可以将光谱分为两组：第一组包含显示弱或中度增殖率的细胞的光谱，第二组包含具有高生长抑制率的细胞的光谱。这些结果很有前途，因为它们表明亚毒性剂量的作用也可以在单细胞水平上进行监测，这可能在患者受益和化疗反应方面具有临床意义。
