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电场通过钙依赖途径调节癌细胞体外表面磷脂酰丝氨酸的暴露。

Electric Fields Regulate In Vitro Surface Phosphatidylserine Exposure of Cancer Cells via a Calcium-Dependent Pathway.

作者信息

Kaynak Ahmet, N'Guessan Kombo F, Patel Priyankaben H, Lee Jing-Huei, Kogan Andrei B, Narmoneva Daria A, Qi Xiaoyang

机构信息

Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH 45221, USA.

Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

出版信息

Biomedicines. 2023 Feb 6;11(2):466. doi: 10.3390/biomedicines11020466.

Abstract

Cancer is the second leading cause of death worldwide after heart disease. The current treatment options to fight cancer are limited, and there is a critical need for better treatment strategies. During the last several decades, several electric field (EF)-based approaches for anti-cancer therapies have been introduced, such as electroporation and tumor-treating fields; still, they are far from optimal due to their invasive nature, limited efficacy and significant side effects. In this study, we developed a non-contact EF stimulation system to investigate the in vitro effects of a novel EF modality on cancer biomarkers in normal (human astrocytes, human pancreatic ductal epithelial -HDPE-cells) and cancer cell lines (glioblastoma U87-GBM, human pancreatic cancer cfPac-1, and MiaPaCa-2). Our results demonstrate that this EF modality can successfully modulate an important cancer cell biomarker-cell surface phosphatidylserine (PS). Our results further suggest that moderate, but not low, amplitude EF induces p38 mitogen-activated protein kinase (MAPK), actin polymerization, and cell cycle arrest in cancer cell lines. Based on our results, we propose a mechanism for EF-mediated PS exposure in cancer cells, where the magnitude of induced EF on the cell surface can differentially regulate intracellular calcium (Ca) levels, thereby modulating surface PS exposure.

摘要

癌症是全球仅次于心脏病的第二大死因。目前对抗癌症的治疗选择有限,迫切需要更好的治疗策略。在过去几十年中,已经引入了几种基于电场(EF)的抗癌治疗方法,如电穿孔和肿瘤治疗电场;然而,由于其侵入性、疗效有限和显著的副作用,它们远非最佳选择。在本研究中,我们开发了一种非接触式EF刺激系统,以研究一种新型EF模式对正常细胞系(人星形胶质细胞、人胰腺导管上皮-HDPE-细胞)和癌细胞系(胶质母细胞瘤U87-GBM、人胰腺癌cfPac-1和MiaPaCa-2)中癌症生物标志物的体外影响。我们的结果表明,这种EF模式可以成功调节一种重要的癌细胞生物标志物——细胞表面磷脂酰丝氨酸(PS)。我们的结果进一步表明,中等幅度而非低幅度的EF会诱导癌细胞系中的p38丝裂原活化蛋白激酶(MAPK)、肌动蛋白聚合和细胞周期停滞。基于我们的结果,我们提出了一种癌细胞中EF介导的PS暴露机制,其中细胞表面诱导的EF大小可以差异调节细胞内钙(Ca)水平,从而调节表面PS暴露。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65f0/9953458/9bf8c83215c4/biomedicines-11-00466-g005.jpg

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本文引用的文献

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