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Therapy of pancreatic cancer with alternating electric fields: Limitations of the method
Bioelectrochemistry ( IF 5 ) Pub Date : 2021-07-01 , DOI: 10.1016/j.bioelechem.2021.107881
Tobias Pfeifer 1 , Liping Bai 1 , Jury Gladkich 1 , Wolfgang Gross 1 , Li Liu 1 , Ingrid Herr 1 , Michael Schaefer 1
Affiliation  

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a poor prognosis. More effective treatment options are urgently needed. The use of physical and weak alternating electric fields (TTFields) can inhibit cell division of PDAC carcinoma and is currently being investigated in clinical trials. Here, we analyzed this new physical treatment under non-ideal conditions such as may occur during patient treatment.

Three established human PDAC cell lines BxPC-3, gemcitabine-resistant BxPC-3 (BxGem), AsPC-1, and a non-malignant primary pancreatic cell line CRL-4023 were treated with TTFields in vitro. MTT assays, electrical impedance measurement, cell staining with Annexin V/7AAD followed by FACS analysis, digital image analysis and immunohistochemistry were performed.

Treatment with TTFields smaller than 0.7 V/cm and field lines in the direction of mitotic spindle orientation significantly inhibited proliferation of all PDAC cells at 150 kHz, but significantly increased viability of AsPC-1 cells at all frequencies between 100 kHz and 300 kHz and that of BxPC-3 and BxGem cells at 250 kHz. Apoptosis or necrosis were not induced. Non-malignant CRL-4023 cells were not affected at 150 kHz.

TTFields damaged PDAC cell lines but even favored their viability at very weak field strength and unfavorable frequency or inadequate field direction.



中文翻译:

用交变电场治疗胰腺癌:该方法的局限性

胰腺导管腺癌(PDAC)是一种高度恶性肿瘤,预后较差。迫切需要更有效的治疗方案。使用物理和弱交变电场 (TTFields) 可以抑制 PDAC 癌的细胞分裂,目前正在临床试验中进行研究。在这里,我们在非理想条件下分析了这种新的物理治疗,例如在患者治疗期间可能发生的情况。

三种已建立的人类 PDAC 细胞系 BxPC-3、吉西他滨抗性 BxPC-3 (BxGem)、AsPC-1 和非恶性原代胰腺细胞系 CRL-4023 在体外用 TTFields 处理。进行 MTT 测定、电阻抗测量、用膜联蛋白 V/7AAD 进行细胞染色,然后进行 FACS 分析、数字图像分析和免疫组织化学。

用小于 0.7 V/cm 的 TTFields 和有丝分裂纺锤体方向的场线处理在 150 kHz 下显着抑制了所有 PDAC 细胞的增殖,但在 100 kHz 和 300 kHz 之间的所有频率下显着增加了 AsPC-1 细胞的活力,并且BxPC-3 和 BxGem 细胞在 250 kHz。未诱导细胞凋亡或坏死。非恶性 CRL-4023 细胞在 150 kHz 时不受影响。

TTFields 损坏了 PDAC 细胞系,但在非常弱的场强和不利的频率或不适当的场方向下甚至有利于它们的生存能力。

更新日期:2021-07-08
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