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基于阻抗筛选的乳腺癌细胞无标记耐药识别

Label-free recognition of drug resistance via impedimetric screening of breast cancer cells.

机构信息

Laboratory of Microsystems (LMIS4), École polytechnique fédérale de Lausanne, Station 17, CH-1015 Lausanne, Switzerland.

出版信息

PLoS One. 2013;8(3):e57423. doi: 10.1371/journal.pone.0057423. Epub 2013 Mar 4.

Abstract

We present a novel study on label-free recognition and distinction of drug resistant breast cancer cells (MCF-7 DOX) from their parental cells (MCF-7 WT) via impedimetric measurements. Drug resistant cells exhibited significant differences in their dielectric properties compared to wild-type cells, exerting much higher extracellular resistance (Rextra ). Immunostaining revealed that MCF-7 DOX cells gained a much denser F-actin network upon acquiring drug resistance indicating that remodeling of actin cytoskeleton is probably the reason behind higher Rextra , providing stronger cell architecture. Moreover, having exposed both cell types to doxorubicin, we were able to distinguish these two phenotypes based on their substantially different drug response. Interestingly, impedimetric measurements identified a concentration-dependent and reversible increase in cell stiffness in the presence of low non-lethal drug doses. Combined with a profound frequency analysis, these findings enabled distinguishing distinct cellular responses during drug exposure within four concentration ranges without using any labeling. Overall, this study highlights the possibility to differentiate drug resistant phenotypes from their parental cells and to assess their drug response by using microelectrodes, offering direct, real-time and noninvasive measurements of cell dependent parameters under drug exposure, hence providing a promising step for personalized medicine applications such as evaluation of the disease progress and optimization of the drug treatment of a patient during chemotherapy.

摘要

我们通过阻抗测量方法,提出了一项关于无标记识别和区分耐药乳腺癌细胞(MCF-7 DOX)和其亲本细胞(MCF-7 WT)的新研究。耐药细胞与野生型细胞相比,在介电性能上存在显著差异,表现出更高的细胞外电阻(Rextra )。免疫染色显示,MCF-7 DOX 细胞在获得耐药性后形成了更加密集的 F-肌动蛋白网络,这表明肌动蛋白细胞骨架的重塑可能是更高 Rextra 的原因,为细胞提供了更强的结构。此外,我们将两种细胞类型都暴露于阿霉素中,能够根据它们截然不同的药物反应来区分这两种表型。有趣的是,在存在低非致死性药物剂量的情况下,阻抗测量发现细胞硬度会呈现浓度依赖性和可逆性增加。结合深入的频率分析,这些发现使我们能够在四个浓度范围内,无需任何标记,区分药物暴露期间的不同细胞反应。总的来说,这项研究强调了使用微电极从亲本细胞中区分耐药表型并评估其药物反应的可能性,为在药物暴露下直接、实时和非侵入性地测量细胞相关参数提供了可能,从而为个性化医疗应用提供了有前景的步骤,例如评估疾病进展和优化化疗期间患者的药物治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae76/3587579/ee1a80b3b7ba/pone.0057423.g001.jpg

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