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通过荧光测定法,将过氧亚硝酸盐作为生物标志物来评估顺铂在miR-125a-5p抗性细胞中的恢复情况。

Peroxynitrite as biomarker to evaluate the rehabilitation of cisplatin in the resistant cells with miR-125a-5p by using fluorescent assay.

作者信息

Lin Jinpei, Lin Shufang, Lin Zengyan, Huang Zhengrong, Li Daliang

机构信息

Department of Integrative Medicine, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province 350014, China.

Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University Qishan Campus, College Town, Fuzhou, Fujian Province 350117, China.

出版信息

Spectrochim Acta A Mol Biomol Spectrosc. 2025 Apr 5;330:125663. doi: 10.1016/j.saa.2024.125663. Epub 2024 Dec 26.

DOI:10.1016/j.saa.2024.125663
PMID:39733707
Abstract

Reactive oxygen species (ROS) play a dual role in the chemotherapy of cancer with cisplatin, providing both anti-tumor effects and contributing to drug resistance at various stages of treatment which seriously affects treatment effectiveness. The detailed mechanism of ROS is urgently necessary to be explored. To address this issue in the non-small-cell lung cancer (NSCLC) with cisplatin-resistance, a reliable assay was developed by synthesizing and characterizing an interesting near-infrared (NIR) ONOO probe BPB with high specificity, quick response (<30 s) and excellent limitation of detection (59 nM), which was further convinced through living cell imaging techniques providing different fluorescence variation between cell and cuvette. All the results revealed that ONOO might be a practical biomarker to comprehend the detail molecular mechanism in cisplatin-resistant A549 cells. The elevated levels of ONOO in cisplatin-resistant A549 cells, accompanied by a significant reduction in fluorescence following the knockout of miR-125a-5p in these cells and strong fluorescence without knockout of miR-125a-5p ignoring the presence of cisplatin. Comparing with cisplatin-resistant cells, the control would provide a rational background and then showed distinct fluorescence from BPB with ONOO toward cisplatin. This assay offers a promising tool for exploring the molecular mechanisms associated with miR-125a-5p and its potential linkage to therapeutic efficacy involving ONOO signaling. By utilizing this innovative assay, researchers can gain valuable insights into the treatment strategies and underlying mechanisms of cisplatin-resistant cancers, which should be beneficial to the therapy of cancers.

摘要

活性氧(ROS)在顺铂治疗癌症中发挥着双重作用,既具有抗肿瘤作用,又在治疗的各个阶段导致耐药性,严重影响治疗效果。迫切需要探索ROS的详细机制。为了解决非小细胞肺癌(NSCLC)顺铂耐药的问题,通过合成和表征一种有趣的近红外(NIR)ONOO探针BPB,开发了一种可靠的检测方法。该探针具有高特异性、快速响应(<30秒)和出色的检测限(59 nM),通过活细胞成像技术进一步证实,该技术可在细胞和比色皿之间提供不同的荧光变化。所有结果表明,ONOO可能是理解顺铂耐药A549细胞详细分子机制的实用生物标志物。顺铂耐药A549细胞中ONOO水平升高,在这些细胞中敲除miR-125a-5p后荧光显著降低,而在不敲除miR-125a-5p的情况下,无论是否存在顺铂,荧光都很强。与顺铂耐药细胞相比,对照组提供了一个合理的背景,然后显示出与含有ONOO的BPB对顺铂的荧光不同。该检测方法为探索与miR-125a-5p相关的分子机制及其与涉及ONOO信号传导的治疗效果的潜在联系提供了一个有前景的工具。通过利用这种创新检测方法,研究人员可以深入了解顺铂耐药癌症的治疗策略和潜在机制,这对癌症治疗应该是有益的。

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