IR spectroscopy reveals effect of non-cytotoxic doses of anti-tumour drug on cancer cells.

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.