Tumor Treating Fields Enhance Temozolomide-Associated Growth Suppression in Glioblastoma Cells and Patient-Derived Organoids Through Cell-Cycle Blockade, Apoptosis, and SMAD-Associated Signaling.
- 1Department of Neurosurgery, The Fourth Affiliated Hospital of Soochow University, Suzhou, China.
- 2Hunan an Tai Kang Cheng Biotechnology Co. Ltd., Changsha, China.
Abstract
Aims
Glioblastoma (GBM) remains difficult to treat despite multimodal therapy. Tumor Treating Fields (TTF) disrupts mitosis and provides clinical benefit in GBM, but the molecular responses associated with TTF and the effects of combining TTF with temozolomide (TMZ) remain incompletely defined.Methods
TMZ, TTF, and TMZ + TTF were evaluated in U251 and SHG140 GBM cells and patient-derived organoids. TTF was applied at 200 kHz and 1.75 V/cm RMS. Viability, colony formation, migration-related phenotypes, apoptosis, cell-cycle distribution, Western blotting, qRT-PCR, RNA-seq, and organoid morphology/immunofluorescence analyses were performed. SB525334 was used to assess SMAD-associated signaling.Results
Combined TMZ + TTF treatment more strongly suppressed cell viability, clonogenic growth, and migration-related phenotypes than either monotherapy, produced greater disruption of organoid structural integrity, and was accompanied by increased cleaved caspase-3 activation and apoptotic populations. RNA-seq identified TTF-associated transcriptomic changes involving chromatin-associated processes, DNA replication, and cell-cycle pathways. TTF was associated with selected SMAD-related signaling changes, G2/M accumulation, altered checkpoint signaling, and enhanced proapoptotic signaling. SB525334 partially attenuated TTF-associated SMAD phosphorylation, growth suppression, and cleaved caspase-3 induction.Conclusion
TTF enhances TMZ-associated antitumor responses in GBM cell lines and organoids, accompanied by cell-cycle blockade, apoptosis-associated changes, and selected SMAD-related signaling responses.
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BibTeX
@article{zhu2026tumor,
title = {{Tumor Treating Fields Enhance Temozolomide-Associated Growth Suppression in Glioblastoma Cells and Patient-Derived Organoids Through Cell-Cycle Blockade, Apoptosis, and SMAD-Associated Signaling.}},
author = {Haiping Zhu and Yingbo Hou and Xuetao Li and Yi Tang and Zuoyu Jiang and Yang Zhang and Xuewen Zhang and Jiaming Du and Yang Zhu and Hanmiao Dong and Yeyang Xu and Ruoyu Sun and Chenyang Li and Zijian Han and Jian Lu and Lingzhi Xiong and Yulun Huang},
journal = {CNS neuroscience \& therapeutics},
year = {2026},
month = oct,
doi = {10.1002/cns.71195},
url = {https://europepmc.org/article/MED/42852958},
note = {CC BY},
}
RIS
TY - JOUR
TI - Tumor Treating Fields Enhance Temozolomide-Associated Growth Suppression in Glioblastoma Cells and Patient-Derived Organoids Through Cell-Cycle Blockade, Apoptosis, and SMAD-Associated Signaling.
AU - Haiping Zhu
AU - Yingbo Hou
AU - Xuetao Li
AU - Yi Tang
AU - Zuoyu Jiang
AU - Yang Zhang
AU - Xuewen Zhang
AU - Jiaming Du
AU - Yang Zhu
AU - Hanmiao Dong
AU - Yeyang Xu
AU - Ruoyu Sun
AU - Chenyang Li
AU - Zijian Han
AU - Jian Lu
AU - Lingzhi Xiong
AU - Yulun Huang
PY - 2026
DA - 2026/10/01
JO - CNS neuroscience & therapeutics
DO - 10.1002/cns.71195
UR - https://europepmc.org/article/MED/42852958
AB - Aims Glioblastoma (GBM) remains difficult to treat despite multimodal therapy. Tumor Treating Fields (TTF) disrupts mitosis and provides clinical benefit in GBM, but the molecular responses associated with TTF and the effects of combining TTF with temozolomide (TMZ) remain incompletely defined.Methods TMZ, TTF, and TMZ + TTF were evaluated in U251 and SHG140 GBM cells and patient-derived organoids. TTF was applied at 200 kHz and 1.75 V/cm RMS. Viability, colony formation, migration-related phenotypes, apoptosis, cell-cycle distribution, Western blotting, qRT-PCR, RNA-seq, and organoid morphology/immunofluorescence analyses were performed. SB525334 was used to assess SMAD-associated signaling.Results Combined TMZ + TTF treatment more strongly suppressed cell viability, clonogenic growth, and migration-related phenotypes than either monotherapy, produced greater disruption of organoid structural integrity, and was accompanied by increased cleaved caspase-3 activation and apoptotic populations. RNA-seq identified TTF-associated transcriptomic changes involving chromatin-associated processes, DNA replication, and cell-cycle pathways. TTF was associated with selected SMAD-related signaling changes, G2/M accumulation, altered checkpoint signaling, and enhanced proapoptotic signaling. SB525334 partially attenuated TTF-associated SMAD phosphorylation, growth suppression, and cleaved caspase-3 induction.Conclusion TTF enhances TMZ-associated antitumor responses in GBM cell lines and organoids, accompanied by cell-cycle blockade, apoptosis-associated changes, and selected SMAD-related signaling responses.
SN - 1755-5930
SN - 1755-5949
ER -