IR spectroscopy reveals effect of non-cytotoxic doses of anti-tumour drug on cancer cells
IR spectroscopy reveals effect of non-cytotoxic doses of anti-tumour drug on cancer cells
复制标题
DOI：
10.1007/s00216-009-3140-y
复制
发表时间：
2009-12-01
影响因子：
4.3
通讯作者：
Sockalingum, Ganesh D.
中科院分区：
文献类型：
--
作者：
Draux, Florence;Jeannesson, Pierre;Sockalingum, Ganesh D.
识别响应于化疗药物治疗的早期细胞事件，特别是在将破坏尽可能多的癌细胞的低剂量下，是患者管理中的重要问题。在这项研究中，我们采用傅里叶变换红外光谱作为一个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。他们暴露于细胞生长抑制剂量（0.1至100 nM，持续24、48和72 h）的吉西他滨，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（千分之一货币符号5%）到中等（类似于23%），再到高（82-95%），而不影响细胞活力。药物处理后，作为剂量和孵育时间的函数，使用台式IR源和同步辐射红外显微镜获得细胞群和单个细胞的光谱。研究表明，在亚致死剂量下可检测到对吉西他滨的光谱细胞反应，并且在细胞群中观察到的效应与单细胞相似。使用聚类分析，光谱可以分为两个主要的组：第一组包含表现出弱或中等增殖率的细胞的光谱，第二组具有来自表现出高生长抑制的细胞的光谱。这些结果是有希望的，因为它们表明亚毒性剂量的作用也可以在单细胞水平上监测，这可能在患者获益和对化疗的反应方面具有临床意义。
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 (a parts per thousand currency sign5%), to moderate (similar to 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.