Abstract
A novel anti-cancer drug sensitivity testing (DST) approach was developed based on in vitro single-cell Raman spectrum intensity (RSI). Generally, the intensity of Raman spectra (RS) for a single living cell treated with drugs positively relates to the sensitivity of the cells to the drugs. In this study, five cancer cell lines (BGC 823, SGC 7901, MGC 803, AGS, and NCI-N87) were exposed to three cytotoxic compounds or to combinations of these compounds, and then they were evaluated for their responses with RSI. The results of RSI were consistent with conventional DST methods. The parametric correlation coefficient for the RSI and Methylthiazolyl tetrazolium assay (MTT) was 0.8558 ± 0.0850, and the coefficient of determination was calculated as R2 = 0.9529 ± 0.0355 for fitting the dose–response curve. Moreover, RSI data for NCI-N87 cells treated by trastuzumab, everolimus (cytostatic), and these drugs in combination demonstrated that the RSI method was suitable for testing the sensitivity of cytostatic drugs. Furthermore, a heterogeneity coefficient H was introduced for quantitative characterization of the heterogeneity of cancer cells treated by drugs. The largest possible variance between RSs of cancer cells were quantitatively obtained using eigenvalues of principal component analysis (PCA). The ratio of H between resistant cells and sensitive cells was greater than 1.5, which suggested the H-value was effective to describe the heterogeneity of cancer cells. Briefly, the RSI method might be a powerful tool for simple and rapid detection of the sensitivity of tumor cells to anti-cancer drugs and the heterogeneity of their responses to these drugs.
Highlights
Anti-tumor drug sensitivity testing (DST) is essential for cancer treatment, especially for individualized cancer therapy (ICT) [1,2,3]
Features of oncosis, including the fact that these cells became bigger than normal living cells, and proteins, peaks correspond to molecular vibrations of cellular components, including nucleic acids, cellular volume obviously increased with the drug concentration (Figure 1)
We proposed a drug sensitivity testing method using Raman spectrum intensity (RSI) which is consistent with conventional
Summary
Anti-tumor drug sensitivity testing (DST) is essential for cancer treatment, especially for individualized cancer therapy (ICT) [1,2,3]. Cancer cells from the same patients or from the same populations of cancer cell lines have significant differences, and this functional and phenotypic heterogeneity is virtually universal. Drug responses in different treatment phases may vary for the same patient [4,5,6,7]. These variations may result in therapeutic failure or toxicity and patient death. ICT is a method directed against cancer heterogeneity, and DST provides an experimental basis of evaluating sensitivity or resistance to ICT in advance [1,8]
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