Chemical activation of Piezo1 to enhance TRAIL-mediated apoptosis in glioblastoma cells

作者

Samantha Knoblauch¹ , Shanay Desai¹ , Jenna Dombroski¹ , Nicole Sarna¹ , Jacob Hope¹ , Michael King¹

1. Vanderbilt University

会议/活动

Biomedical Engineering Society 2022 Annual Meeting, October 2022 (San Antonio, TX, United States)

海报摘要

Glioblastoma multiforme (GBM) treatment with the current standard of care, temozolomide (TMZ), may be ineffective if damaged tumor cells undergo DNA repair or acquire mutations that inactivate transcription factor p53, leading to poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in multiple tumor types through a transcription-independent mechanism. GBM is particularly resistant to TRAIL, but studies have found that activation of the mechanoreceptor Piezo1 can induce TRAIL sensitization in other cancer cell lines. This study examines the effects and mechanism of Piezo1 chemical activation via Yoda1 on TRAIL-mediated apoptosis in GBM. We demonstrate that a Yoda1 + TRAIL combination therapy significantly increases apoptosis in two GBM cell lines. Further, cells known to be resistant to TMZ had higher levels of Piezo1 expression and were more susceptible to our treatment. The results of this study demonstrate the efficacy of overcome TMZ resistance in GBM using TRAIL and Piezo1 activation.

关键词

Apoptosis, Assays, Cancer, Cells, Polarization, Mechanobiology

研究领域

Bioengineering, Biological Sciences

参考文献

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基金

1. National Institutes of Health (No. CA256054)

补充材料

暂无数据

附加信息

利益冲突

No competing interests were disclosed.

数据可用性声明

The datasets generated during and / or analyzed during the current study are available from the corresponding author on reasonable request.

知识共享许可协议

Copyright © 2023 Knoblauch et al. This is an open access work distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.