Yu Tong, Jadhav Archana Chandrabhan, Xu Jiabao, Harris Adrian L, Nair Venugopal, Huang Wei E
Department of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, UK.
Beamline B24, Diamond Light Source, Harwell Science and Innovation Campus, Oxfordshire OX11 0DE, UK.
Cancers (Basel). 2023 Jan 28;15(3):811. doi: 10.3390/cancers15030811.
Newcastle disease virus (NDV) is an oncolytic agent against various types of mammalian cancers. As with all cancer therapies, the development of cancer resistance, both innate and acquired, is becoming a challenge. In this study, we investigated persistently NDV-infected Caco-2 colon cancer cells, designated as virus-resistant (VR) Caco-2 cells, which were then able to resist NDV-mediated oncolysis. We applied single-cell Raman spectroscopy, combined with deuterium isotope probing (Raman-DIP) techniques, to investigate the metabolic adaptations and dynamics in VR Caco-2 cells. A linear discriminant analysis (LDA) model demonstrated excellent performance in differentiating VR Caco-2 from Caco-2 cells at single-cell level. By comparing the metabolic profiles in a time-resolved manner, the de novo synthesis of proteins and lipids was found upregulated, along with decreased DNA synthesis in VR Caco-2. The results suggest that VR Caco-2 cells might reprogram their metabolism and divert energy from proliferation to protein synthesis and lipidic modulation. The ability to identify and characterise single resistant cells among a population of cancer cells would help develop a deeper understanding of the resistance mechanisms and better tactics for developing effective cancer treatment.
新城疫病毒（NDV）是一种针对多种类型哺乳动物癌症的溶瘤剂。与所有癌症治疗方法一样，癌症固有抗性和获得性抗性的产生正成为一项挑战。在本研究中，我们研究了持续感染NDV的Caco-2结肠癌细胞，将其命名为病毒抗性（VR）Caco-2细胞，这些细胞随后能够抵抗NDV介导的溶瘤作用。我们应用单细胞拉曼光谱结合氘同位素探测（拉曼-DIP）技术，来研究VR Caco-2细胞中的代谢适应性和动态变化。线性判别分析（LDA）模型在单细胞水平上区分VR Caco-2细胞和Caco-2细胞方面表现出优异的性能。通过以时间分辨的方式比较代谢谱，发现VR Caco-2细胞中蛋白质和脂质的从头合成上调，同时DNA合成减少。结果表明，VR Caco-2细胞可能会重新编程其代谢，将能量从增殖转移到蛋白质合成和脂质调节。在一群癌细胞中识别和表征单个抗性细胞的能力，将有助于更深入地了解抗性机制，并为开发有效的癌症治疗方法提供更好的策略。
