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Molecules 2018, 23(11), 2903; https://doi.org/10.3390/molecules23112903

Anti-Cancer Drug Sensitivity Assay with Quantitative Heterogeneity Testing Using Single-Cell Raman Spectroscopy

1
Key Laboratory for the Physics and Chemistry of Nanodevices, School of Electronics Engineering and Computer Science, Peking University, No.5 Yiheyuan Road, Beijing 100871, China
2
Beijing Institute of Biomedicine, No.15 Xinjiangongmen Road, Beijing 100091, China
3
Academy for Advanced Interdisciplinary Studies, Peking University, No.5 Yiheyuan Road, Beijing 100871, China
*
Author to whom correspondence should be addressed.
Received: 27 September 2018 / Revised: 1 November 2018 / Accepted: 5 November 2018 / Published: 7 November 2018
(This article belongs to the Special Issue Raman Spectroscopy: A Spectroscopic 'Swiss-Army Knife')
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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. View Full-Text
Keywords: raman spectroscopy; medical optics; biotechnology; drug sensitivity testing; cancer cells raman spectroscopy; medical optics; biotechnology; drug sensitivity testing; cancer cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Zhang, Y.; Xu, J.; Yu, Y.; Shang, W.; Ye, A. Anti-Cancer Drug Sensitivity Assay with Quantitative Heterogeneity Testing Using Single-Cell Raman Spectroscopy. Molecules 2018, 23, 2903.

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