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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

Enhancement of reactive oxygen species production in triple negative breast cancer cells treated with electric pulses and resveratrol.

作者信息

Giri Pragatheiswar, Camarillo Ignacio G, Sundararajan Raji

机构信息

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

Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.

出版信息

Explor Target Antitumor Ther. 2023;4(1):42-56. doi: 10.37349/etat.2023.00122. Epub 2023 Feb 28.

Abstract

AIM

Triple negative breast cancer (TNBC) is difficult to treat since it lacks all the three most commonly targeted hormone receptors. Patients afflicted with TNBC are treated with platinum core chemotherapeutics, such as cisplatin. Despite the initial effective anticancer effects of cisplatin, TNBC attenuates its effect and develops resistance eventually, which results in tumor reoccurrence. Hence, there is a critical demand for effective, alternative, and natural ways to treat TNBC. Towards this, a promising technique for inhibiting TNBC cell proliferation involves promoting the production of reactive oxygen species (ROS), which triggers pro-apoptotic caspases 9 and 3. Resveratrol (RESV), an active bio compound found in naturally available fruits, such as grapes, is utilized in this research for that. In addition, electrochemotherapy (ECT), which involves the application of electrical pulses (EP), was utilized to enhance the uptake of RESV.

METHODS

MDA-MB-231, human TNBC cells were treated with/out RESV, and eight 600-1,000 V/cm, 100 μs pulses at 1 Hz. The cells were characterized by using various assays, including viability assay, and ROS assay.

RESULTS

A TNBC cell viability of as low as 20% was obtained at 24 h (it was 13% at 60 h), demonstrating the potential of this novel treatment. ROS production was the highest in the combination of EP at 1,000 V/cm along with RESV at 100 μmol/L.

CONCLUSIONS

Results indicate that RESV has the potential as an anti-TNBC agent and that EP + RESV can significantly enhance the cell death to reduce MDA-MB-231 cell viability by increasing ROS production and triggering apoptosis.

摘要

目的

三阴性乳腺癌(TNBC)因缺乏三种最常见的靶向激素受体而难以治疗。患有TNBC的患者接受铂类核心化疗药物治疗,如顺铂。尽管顺铂最初具有有效的抗癌作用,但TNBC会减弱其效果并最终产生耐药性,导致肿瘤复发。因此,迫切需要有效、替代且天然的方法来治疗TNBC。为此,一种有前景的抑制TNBC细胞增殖的技术是促进活性氧(ROS)的产生,ROS会触发促凋亡半胱天冬酶9和3。白藜芦醇(RESV)是一种存在于天然水果(如葡萄)中的活性生物化合物,本研究中使用它来实现这一目的。此外,电化学疗法(ECT),即施加电脉冲(EP),被用于增强RESV的摄取。

方法

用/不用RESV处理人TNBC细胞MDA-MB-231,并施加八个600 - 1000 V/cm、100 μs、1 Hz的脉冲。通过各种检测方法对细胞进行表征,包括活力检测和ROS检测。

结果

24小时时TNBC细胞活力低至20%(60小时时为13%),证明了这种新疗法的潜力。在1000 V/cm的EP与100 μmol/L的RESV联合使用时,ROS产生量最高。

结论

结果表明RESV有作为抗TNBC药物的潜力,并且EP + RESV可通过增加ROS产生和触发凋亡显著增强细胞死亡,从而降低MDA-MB-231细胞活力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32b2/10017187/a6e0d1b9e870/etat-04-1002122-g001.jpg

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