对顺铂敏感和耐药的间充质三阴性乳腺癌的新化疗方法:振动显微光谱法评估细胞反应。

IF 6.7 1区 化学 Q1 CHEMISTRY, ANALYTICAL
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引用次数: 0

摘要

三阴性乳腺癌(TNBC)是最具侵袭性的乳腺肿瘤类型,预后最差。针对TNBC的新化疗药物是必不可少的,其目的是在抑制细胞生长、减少血管生成和侵袭性方面具有更高的疗效,同时降低获得性耐药和有害副作用。在本研究中,采用拉曼和傅里叶变换红外(FTIR)显微光谱技术评估了三核钯-亚精胺复合物对人体健康和间质TNBC细胞的影响,并将结果与临床使用的药物顺铂进行了比较。为了了解药物在分子水平上的代谢影响并确定主要的生物标志物,对振动数据进行了无监督的多变量分析(主成分分析和层次聚类分析)。结果表明,新型钯(Pd)制剂对细胞脂质的影响高于铂(Pt)化合物(顺铂),而铂(Pt)化合物对蛋白质的影响更大。除脂质外,Pd-agent对B-DNA天然构象到Z-或a - dna的构象变化有更大的影响。这表明这些金属配合物具有不同的细胞毒性途径。在顺铂敏感细胞和顺铂耐药细胞的比较中,Pd-agent对顺铂敏感细胞DNA的δ opackbone、脂质的δCH2和苯丙氨酸的δ sccring的影响更为显著,而在顺铂耐药细胞中,蛋白质是受影响最大的细胞成分。这些结果提供了恶性肿瘤特异性的光谱特征,导致了药物治疗和未治疗细胞之间的区别。这一知识对于合理设计效率更高、毒性更低的改良药物至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

New Chemotherapeutic Approaches to Treatment of Mesenchymal Triple-Negative Breast Cancer-Sensitive and Resistant to Cisplatin: Assessment of Cellular Response by Vibrational Microspectroscopy

New Chemotherapeutic Approaches to Treatment of Mesenchymal Triple-Negative Breast Cancer-Sensitive and Resistant to Cisplatin: Assessment of Cellular Response by Vibrational Microspectroscopy

Triple-negative breast cancer (TNBC) is the most aggressive type of breast tumor with the worst prognosis. New chemotherapeutic agents against TNBC are essential, aiming at a higher efficacy regarding cell growth inhibition and decreased angiogenesis and invasiveness coupled to lower acquired resistance and deleterious side effects. In this study, Raman and Fourier Transform Infrared (FTIR) microspectroscopies were applied to assess the impact of a trinuclear palladium-spermidine complex on human healthy and mesenchymal TNBC cells, with the results being compared to the clinically used drug cisplatin. To understand the metabolic impact of the drugs at the molecular level and identify the main biomarkers, unsupervised multivariate analysis of the data (Principal Component Analysis and Hierarchical Cluster Analysis) was applied to the vibrational data. The results revealed that the new palladium (Pd) agent had a higher effect on the cellular lipids relative to the platinum (Pt) compound (cisplatin), while the latter showed a stronger impact on the proteins. Besides lipids, Pd-agent showed a higher impact in conformational changes from the B-DNA native conformation to either Z- or A-DNA. This suggests the occurrence of distinct pathways of cytotoxicity for these metal complexes. Also, when comparing cisplatin-sensitive to cisplatin-resistant cells, Pd-agent had a more significant impact on νOPObackbone from DNA, δCH2 from lipids and νsCCring from phenylalanine of cisplatin-sensitive cells, while in cisplatin-resistant cells, proteins were the most affected cell components. These results provided spectral features specific to malignancy that led to discrimination between drug-treated and untreated cells. This knowledge is essential for the rational design of improved drugs with a higher efficiency coupled to lower toxicity.

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来源期刊
Analytical Chemistry
Analytical Chemistry 化学-分析化学
CiteScore
12.10
自引率
12.20%
发文量
1949
审稿时长
1.4 months
期刊介绍: Analytical Chemistry, a peer-reviewed research journal, focuses on disseminating new and original knowledge across all branches of analytical chemistry. Fundamental articles may explore general principles of chemical measurement science and need not directly address existing or potential analytical methodology. They can be entirely theoretical or report experimental results. Contributions may cover various phases of analytical operations, including sampling, bioanalysis, electrochemistry, mass spectrometry, microscale and nanoscale systems, environmental analysis, separations, spectroscopy, chemical reactions and selectivity, instrumentation, imaging, surface analysis, and data processing. Papers discussing known analytical methods should present a significant, original application of the method, a notable improvement, or results on an important analyte.
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