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钙电穿孔诱导横纹肌肉瘤细胞死亡的主要类型为细胞凋亡。

Apoptosis as the main type of cell death induced by calcium electroporation in rhabdomyosarcoma cells.

机构信息

Faculty of Pharmacy, Department of Molecular and Cellular Biology, Wroclaw Medical University, Poland; Department of Animal Developmental Biology, Institute of Experimental Biology, University of Wroclaw, Wroclaw, Poland.

Faculty of Pharmacy, Department of Molecular and Cellular Biology, Wroclaw Medical University, Poland.

出版信息

Bioelectrochemistry. 2020 Dec;136:107592. doi: 10.1016/j.bioelechem.2020.107592. Epub 2020 Jul 2.

Abstract

Calcium electroporation (CaEP) has been previously reported as an effective method of rhabdomyosarcoma cells reduction. CaEP causes temporary cell membrane permeabilization with simultaneous calcium ions influx. A rapid influx of calcium ions leads to mitochondrial overload by Ca, loss of mitochondrial membrane potential causing cytochrome c release, caspase cascade activation and, as a consequence, cell death. This study was conducted on two cell lines: normal muscle cells (C2C12) and rhabdomyosarcoma cells (RD), which showed different cellular responses to CaEP. Our study defined apoptosis as the main cell death type occurring after CaEP in RD cells. Increased activity of caspase 3/7, Parp-1 and cleaved Parp-1 were proven in the case of RD cells. RD cells compartment rearrangement was observed in the time-lapse by holotomographic microscopy (HTM). C2C12 cells were less sensitive to electroporation and increased Ca concentration, and viability was maintained at the level of control cells, only slight changes in pro-apoptotic factors were observed. The results reveal CaEP as a promising therapeutic approach in cancers which develop from muscle tissue.

摘要

钙电穿孔(CaEP)已被报道为减少横纹肌肉瘤细胞的有效方法。CaEP 导致细胞膜暂时通透性增加,同时钙离子内流。钙离子的快速内流导致线粒体超载,线粒体膜电位丧失导致细胞色素 c 释放,半胱天冬酶级联激活,最终导致细胞死亡。本研究针对两种细胞系进行:正常肌肉细胞(C2C12)和横纹肌肉瘤细胞(RD),它们对 CaEP 的细胞反应不同。我们的研究将细胞凋亡定义为 CaEP 后 RD 细胞发生的主要细胞死亡类型。在 RD 细胞中,证实了 caspase 3/7、Parp-1 和 cleaved Parp-1 的活性增加。通过全层显微镜(HTM)在延时观察中观察到 RD 细胞隔室重排。C2C12 细胞对电穿孔和钙离子浓度增加的敏感性较低,活力保持在对照细胞的水平,仅观察到促凋亡因子的轻微变化。结果表明,CaEP 是一种有前途的治疗方法,适用于源自肌肉组织的癌症。

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