Farhane Zeineb, Bonnier Franck, Howe Orla, Casey Alan, Byrne Hugh J
FOCAS Research Institute, Dublin Institute of Technology, Kevin Street, Dublin 8, Ireland.
School of Physics, Dublin Institute of Technology, Kevin Street, Dublin 8, Ireland.
J Biophotonics. 2018 Jan;11(1). doi: 10.1002/jbio.201700060. Epub 2017 Jun 21.
Raman micro-spectroscopy is a non-invasive analytical tool, whose potential in cellular analysis and monitoring drug mechanisms of action has already been demonstrated, and which can potentially be used in pre-clinical and clinical applications for the prediction of chemotherapeutic efficacy. To further investigate such potential clinical application, it is important to demonstrate its capability to differentiate drug mechanisms of action and cellular resistances. Using the example of Doxorubicin (DOX), in this study, it was used to probe the cellular uptake, signatures of chemical binding and subsequent cellular responses, of the chemotherapeutic drug in two lung cancer cell lines, A549 and Calu-1. Multivariate statistical analysis was used to elucidate the spectroscopic signatures associated with DOX uptake and subcellular interaction. Biomarkers related to DNA damage and repair, and mechanisms leading to apoptosis were also measured and correlated to Raman spectral profiles. Results confirm the potential of Raman spectroscopic profiling to elucidate both drug kinetics and pharmacodynamics and differentiate cellular drug resistance associated with different subcellular accumulation rates and subsequent cellular response to DNA damage, pointing towards a better understanding of drug resistance for personalised targeted treatment.
拉曼显微光谱是一种非侵入性分析工具，其在细胞分析和监测药物作用机制方面的潜力已经得到证实，并且有可能用于临床前和临床应用中预测化疗疗效。为了进一步研究这种潜在的临床应用，证明其区分药物作用机制和细胞耐药性的能力很重要。在本研究中，以阿霉素（DOX）为例，用其探测化疗药物在两种肺癌细胞系A549和Calu-1中的细胞摄取、化学结合特征及随后的细胞反应。采用多元统计分析来阐明与DOX摄取和亚细胞相互作用相关的光谱特征。还测量了与DNA损伤和修复相关的生物标志物以及导致细胞凋亡的机制，并将其与拉曼光谱图谱相关联。结果证实了拉曼光谱分析在阐明药物动力学和药效学以及区分与不同亚细胞积累速率相关的细胞耐药性和随后细胞对DNA损伤的反应方面的潜力，这有助于更好地理解耐药性以进行个性化靶向治疗。
