Discrimination between drug-resistant and non-resistant human melanoma cell lines by FTIR spectroscopy

Abstract

We investigated the ability of FTIR-microscopy to define spectral changes between drug-sensitive and drug-resistant human melanoma cells. As a model system, a resistant melanoma cell line (GAC) was selected with cisplatin from parental (GA) cells. Using Fourier transform infrared spectroscopy (FTIR) we investigated the ability to differentiate between the resistant variant derived from the sensitive parental cell line, in the absence of cisplatin. We determined and validated spectral parameters (biomarkers) that differentiated between the two cell lines. By applying the principal component analysis (PCA) model, we reduced the original data size to six principal components. We detected a significant and consistent increase in the cell's DNA/RNA ratio as well as an increase in the lipid/protein ratio in the resistant cells. These results strongly support the potential of developing FTIR microspectroscopy as a simple, reagent-free method for the identification of drug-resistant cells. Rapid detection of tumors resistant to a particular drug, should contribute to the ability of the physician to choose an effective treatment protocol.

In situ Fourier transform infrared analysis of live cells' response to doxorubicin

“…Subtle differences in cell spectra have been used to distinguish cells in different stages in the cell cycle [2], apoptotic cells [3] or cell lines [4,5], to identify cancer cells [6], and to predict the aggressiveness of cancer cells [7]. Several studies have shown a relationship between the mode of action of chemotherapy drugs and changes in FTIR spectra of dried cells [8][9][10], as well as differences in FTIR spectra of drug-resistant and drug-sensitive cells [11][12][13]. In these studies cells were treated with a mildly cytotoxic or cytostatic concentration of drug, generally the IC 50 value for the drug toxicity, and were then collected and dried prior FTIR analysis, as water causes a strong interference in FTIR analysis.…”

Tracing overlapping biological signals in mid-infrared using colonic tissues as a model system

“…However, it has an intrinsic complexity associated with overlapping signals from different metabolites that can simultaneously absorb making it difficult to often assign variations in absorbance at a particular wavenumber to a single metabolite. To overcome this problem other than taking very specific intensities corresponding to known metabolites that are expected to vary due to biological variations, advanced methodologies for spectral analyses have been adopted[15,18]. These have been useful to partly increase the sensitivity and specificity of spectral analyses especially in cancer diagnostics.…”

From structure to cellular mechanism with infrared microspectroscopy

“…Epifluorescence microscopy was used to determine the stage of apoptosis while protein oxidation and degradation were observed with FTIR microspectroscopy [35]. Since then, high-resolution FTIR microspectroscopy has been widely used, for example to evaluate protein structure in fibroblasts, giant sarcoma cells [36], and mitotic cells [37], amyloid formation in neuronal infection [38], drug resistance in human melanoma cells [39], and epithelial cells for cervical cancer screening [40]. …”