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顺铂电化学疗法显著下调 MDA-MB-231-人三阴性乳腺癌细胞中的关键热休克蛋白。

Cisplatin-based Electrochemotherapy Significantly Downregulates Key Heat Shock Proteins in MDA-MB-231-Human Triple-Negative Breast Cancer Cells.

机构信息

School of Engineering Technology, Purdue University, West Lafayette, IN, 47907, USA.

Aarupdaia Veedu Medical College, Pondicherry, India.

出版信息

Appl Biochem Biotechnol. 2022 Jan;194(1):517-528. doi: 10.1007/s12010-021-03703-9. Epub 2021 Oct 12.

DOI:10.1007/s12010-021-03703-9
PMID:34637110
Abstract

Heat shock proteins (HSPs) are available and/or induced for the survival of all organisms, including eukaryotic, prokaryotic, and plants, from higher temperature stresses. They are the chaperone proteins that protect all cells against heat, as the name implies. In addition to thermal stress, they also protect them from chemical, physical, and other stresses, including exposure to oxidative stress, nutritional deficiencies, ultraviolet radiation, ethanol, viral infection, ischemia-reperfusion injury, and cancer-related stresses. They are classified based on their molecular weights in kDa, such as HSP90 and HSP70. In our label-free, high-throughput, quantitative LC-MS/MS-based proteomic studies of MDA-MB-231, human, triple-negative breast cancer cells, treated with electrical pulses (EP) and cisplatin (CsP), we identified a number of HSPs, such as HSP90AA1, and others to be significantly downregulated in EP + CsP, compared to CsP alone. This indicates that cells will undergo apoptotic cell death and hence could cause effective cancer cure/treatment. Considering that over 2 million new cases and over 600,000 deaths in 2020, of which ~ 15% are TNBC, heat shock proteins could be the untapped resources, available for the next biomarkers and/or inhibitors for new/additional therapies.

摘要

热休克蛋白(HSPs)是所有生物体(包括真核生物、原核生物和植物)在高温胁迫下生存的可用或诱导产生的伴侣蛋白。顾名思义,它们可以保护所有细胞免受高温的影响。除了热应激外,它们还可以保护细胞免受化学、物理和其他应激,包括暴露于氧化应激、营养缺乏、紫外线辐射、乙醇、病毒感染、缺血再灌注损伤和与癌症相关的应激。它们根据其在 kDa 中的分子量进行分类,例如 HSP90 和 HSP70。在我们对 MDA-MB-231、人类、三阴性乳腺癌细胞进行的无标记、高通量、基于 LC-MS/MS 的定量蛋白质组学研究中,我们发现了一些 HSPs,如 HSP90AA1 和其他 HSPs,与单独使用顺铂(CsP)相比,电脉冲(EP)和顺铂(CsP)处理后的表达水平显著下调。这表明细胞将经历细胞凋亡,因此可能导致有效的癌症治愈/治疗。考虑到 2020 年有超过 200 万例新发病例和超过 60 万例死亡,其中约 15%是三阴性乳腺癌,热休克蛋白可能是未开发的资源,可用于新/附加治疗的下一个生物标志物和/或抑制剂。

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本文引用的文献

1
Electrochemotherapy in the treatment of cutaneous malignancy: Outcomes and subgroup analysis from the cumulative results from the pan-European International Network for Sharing Practice in Electrochemotherapy database for 2482 lesions in 987 patients (2008-2019).电化学疗法治疗皮肤恶性肿瘤:来自泛欧国际电化学疗法实践共享网络数据库 987 例患者 2482 个病灶的累积结果的汇总分析(2008-2019 年)。
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电脉冲和白藜芦醇处理的三阴性乳腺癌细胞中活性氧生成的增强
Explor Target Antitumor Ther. 2023;4(1):42-56. doi: 10.37349/etat.2023.00122. Epub 2023 Feb 28.
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Antitumor Potential of Sericite Treatment Mediated by Cell Cycle Arrest in Triple-Negative MDA-MB231 Breast Cancer Cells.绢云母处理通过使三阴性MDA-MB231乳腺癌细胞的细胞周期停滞介导的抗肿瘤潜力。
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