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内质网应激和未折叠蛋白反应在癌细胞和非癌细胞中的调节

Modulation of endoplasmic reticulum stress and the unfolded protein response in cancerous and noncancerous cells.

作者信息

Purnell Marcy C, Butawan Matthew Ba, Bingol Kemal, Tolley Elizabeth A, Whitt Michael A

机构信息

Department of Microbiology, Immunology and Biochemistry, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA.

The Loewenberg College of Nursing, The University of Memphis, Memphis, TN, USA.

出版信息

SAGE Open Med. 2018 Jun 20;6:2050312118783412. doi: 10.1177/2050312118783412. eCollection 2018.

Abstract

OBJECTIVES

The bio-field array is a device that generates a dielectrophoretic electromagnetic field when placed in a hypotonic saline solution and a direct current of approximately 3 A is applied. It is known that cell physiology is guided by bioelectrical properties, and there is a significant growth inhibition in cancerous (MDA-MB-231) cells that are grown in media that has been reconstituted with the saline that has been exposed to the bio-field array direct current dielectrophoretic electromagnetic field, alternatively there is no growth inhibition noted in noncancerous cells (MCF-10A) when grown in the bio-field array direct current dielectrophoretic electromagnetic field treated versus control media.

METHODS

To examine the basis for selective growth inhibition in human breast carcinoma, we employed cell death assays, cell cycle assays, microarray analysis and reverse transcription-quantitative polymerase chain reaction.

RESULTS

We found a large transcriptional reprogramming in the cell lines and of the genes affected, those involved in endoplasmic reticulum stress and the unfolded protein response pathways showed some of the most dramatic changes. Cancerous cells grown in media that has been reconstituted with a hypotonic saline solution that has been exposed to the bio-field array direct current dielectrophoretic electromagnetic field show a significant and strong upregulation of the apoptotic arms of the unfolded protein response while the noncancerous cells show a decrease in endoplasmic reticulum stress via microarray analyses and reverse transcription-quantitative polymerase chain reaction.

CONCLUSION

The bio-field array shows potential to initiate apoptosis in cancerous cells while relieving cell stress in noncancerous cells in vitro. These studies lay a foundation for nurses to conduct future in vivo models for the possible development of future adjunct treatments in chronic disease.

摘要

目的

生物场阵列是一种装置,当置于低渗盐溶液中并施加约3 A的直流电时,会产生介电泳电磁场。已知细胞生理学受生物电特性的引导,在用暴露于生物场阵列直流电介电泳电磁场的盐溶液重构的培养基中生长的癌性(MDA - MB - 231)细胞存在显著的生长抑制,相反,在生物场阵列直流电介电泳电磁场处理的培养基与对照培养基中生长的非癌性细胞(MCF - 10A)未观察到生长抑制。

方法

为了研究人乳腺癌中选择性生长抑制的基础,我们采用了细胞死亡检测、细胞周期检测、微阵列分析和逆转录定量聚合酶链反应。

结果

我们发现细胞系以及受影响的基因存在大量转录重编程,参与内质网应激和未折叠蛋白反应途径的基因显示出一些最显著的变化。通过微阵列分析和逆转录定量聚合酶链反应发现,在用暴露于生物场阵列直流电介电泳电磁场的低渗盐溶液重构的培养基中生长的癌细胞,未折叠蛋白反应的凋亡途径显著且强烈上调,而非癌性细胞的内质网应激则有所降低。

结论

生物场阵列在体外显示出诱导癌细胞凋亡同时减轻非癌性细胞应激的潜力。这些研究为护士开展未来体内模型研究奠定了基础,以便为慢性病未来辅助治疗的可能发展提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d154/6024343/66fbe18e1d81/10.1177_2050312118783412-fig1.jpg

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