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交变电场对有丝分裂纺锤体的破坏导致癌细胞中染色体分离异常和有丝分裂灾难。

Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells.

作者信息

Giladi Moshe, Schneiderman Rosa S, Voloshin Tali, Porat Yaara, Munster Mijal, Blat Roni, Sherbo Shay, Bomzon Zeev, Urman Noa, Itzhaki Aviran, Cahal Shay, Shteingauz Anna, Chaudhry Aafia, Kirson Eilon D, Weinberg Uri, Palti Yoram

机构信息

Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.

出版信息

Sci Rep. 2015 Dec 11;5:18046. doi: 10.1038/srep18046.

DOI:10.1038/srep18046
PMID:26658786
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4676010/
Abstract

Tumor Treating Fields (TTFields) are low intensity, intermediate frequency, alternating electric fields. TTFields are a unique anti-mitotic treatment modality delivered in a continuous, noninvasive manner to the region of a tumor. It was previously postulated that by exerting directional forces on highly polar intracellular elements during mitosis, TTFields could disrupt the normal assembly of spindle microtubules. However there is limited evidence directly linking TTFields to an effect on microtubules. Here we report that TTFields decrease the ratio between polymerized and total tubulin, and prevent proper mitotic spindle assembly. The aberrant mitotic events induced by TTFields lead to abnormal chromosome segregation, cellular multinucleation, and caspase dependent apoptosis of daughter cells. The effect of TTFields on cell viability and clonogenic survival substantially depends upon the cell division rate. We show that by extending the duration of exposure to TTFields, slowly dividing cells can be affected to a similar extent as rapidly dividing cells.

摘要

肿瘤治疗电场（TTFields）是低强度、中频交变电场。TTFields是一种独特的抗有丝分裂治疗方式，以连续、非侵入性的方式作用于肿瘤区域。此前推测，在有丝分裂过程中，TTFields通过对高度极化的细胞内成分施加定向力，可能会破坏纺锤体微管的正常组装。然而，直接将TTFields与对微管的影响联系起来的证据有限。在此我们报告，TTFields降低了聚合微管蛋白与总微管蛋白的比例，并阻止了有丝分裂纺锤体的正常组装。TTFields诱导的异常有丝分裂事件导致染色体分离异常、细胞多核化以及子细胞的半胱天冬酶依赖性凋亡。TTFields对细胞活力和克隆存活的影响很大程度上取决于细胞分裂速率。我们表明，通过延长暴露于TTFields的持续时间，缓慢分裂的细胞可以受到与快速分裂细胞相似程度的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/73a738279e63/srep18046-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/8a54810e2b32/srep18046-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/8bb0eda3d501/srep18046-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/a213647fadbc/srep18046-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/fdf28f91367a/srep18046-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/e0483f63eb40/srep18046-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/562ef65609e6/srep18046-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/73a738279e63/srep18046-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/8a54810e2b32/srep18046-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/8bb0eda3d501/srep18046-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/a213647fadbc/srep18046-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/fdf28f91367a/srep18046-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/e0483f63eb40/srep18046-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/562ef65609e6/srep18046-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/4676010/73a738279e63/srep18046-f7.jpg

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Clinical practice experience with NovoTTF-100A™ system for glioblastoma: The Patient Registry Dataset (PRiDe).用于胶质母细胞瘤的NovoTTF-100A™系统的临床实践经验：患者登记数据集（PRiDe）
Semin Oncol. 2014 Oct;41 Suppl 6:S4-S13. doi: 10.1053/j.seminoncol.2014.09.010. Epub 2014 Sep 16.
3
Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo.
成纤维细胞生长因子受体（FGFR）抑制作为一种使胶质母细胞瘤干细胞对肿瘤治疗电场敏感的新治疗策略。
Cell Death Discov. 2025 Jun 4;11(1):265. doi: 10.1038/s41420-025-02542-5.
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Tumor-Treating Fields Alter Nanomechanical Properties of Pancreatic Ductal Adenocarcinoma Cells Co-Cultured with Extracellular Matrix.肿瘤治疗电场改变与细胞外基质共培养的胰腺导管腺癌细胞的纳米力学特性。
J Funct Biomater. 2025 May 3;16(5):160. doi: 10.3390/jfb16050160.
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