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Published on: October 27, 2014
Tumor suppressive effect of low-frequency repetitive transcranial magnetic stimulation on glioblastoma progression
Seongmoon Jo1, Sang Hee Im2, Sung Hoon Kim3
1Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, South Korea; Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea; Division of Hematology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Abstract:
Repetitive transcranial magnetic stimulation (rTMS) is used as a non-invasive treatment for various diseases, and its potential application in cancer treatment has been proposed by researchers. However, the precise mechanisms and effects of rTMS on many types of cancer, including glioblastoma (GBM), remain largely unknown. This study aimed to investigate the effects of low-frequency rTMS on in vitro and in vivo GBM models and to elucidate an underlying biological mechanism of rTMS on GBM. In vitro and in vivo GBM models were treated with low-frequency rTMS (0.5 Hz, 10 min per day), and the effects of rTMS were assessed using various assays, including CCK-8 assay, sphere formation assay, 3D invasion assay, RT-qPCR, Western blot, immunohistochemistry, TUNEL assay, MRI, and IVIS. The results showed that treatment of GBM models in vitro with low-frequency rTMS significantly inhibited cell proliferation. Transcriptome array analysis revealed a substantial downregulation of FLNA and FLNC expression after low-frequency rTMS treatment. Moreover, in an in vitro GBM tumor sphere model, low-frequency rTMS suppressed the activation of EGFR and EphA2, inhibited ERK/JNK/p38 and PI3K/AKT/mTOR pathways, and induced apoptosis. Low-frequency rTMS also suppressed the invasion of GBM by downregulating MMP2 and MMP9 expression. Additionally, in an in vivo GBM model, low-frequency rTMS suppressed GBM progression by downregulating FLNA and FLNC expression. The results demonstrated that low-frequency rTMS could be a potential treatment for GBM, achieved by downregulating FLNA and FLNC expression. This study sheds light on the potential for rTMS as a therapeutic strategy for glioblastoma as well as other types of cancers.
Insights
Low-frequency repetitive transcranial magnetic stimulation (rTMS) effectively inhibited glioblastoma (GBM) cell proliferation and invasion in vitro and in vivo. This non-invasive treatment suppressed GBM progression by downregulating Filamin A (FLNA) and Filamin C (FLNC) expression.
Area of Science:
- Neuroscience
- Oncology
- Biomedical Engineering
Background:
- Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique with proposed applications in cancer therapy.
- The precise mechanisms and efficacy of rTMS, particularly low-frequency rTMS, in treating glioblastoma (GBM) remain largely unexplored.
Purpose of the Study:
- To investigate the effects of low-frequency rTMS on in vitro and in vivo GBM models.
- To elucidate the underlying biological mechanisms of rTMS action on GBM.
Main Methods:
- Utilized in vitro and in vivo GBM models treated with low-frequency rTMS (0.5 Hz, 10 min/day).
- Assessed effects using CCK-8, sphere formation, 3D invasion assays, RT-qPCR, Western blot, immunohistochemistry, TUNEL assay, MRI, and IVIS.
- Analyzed transcriptome arrays to identify molecular changes.
Main Results:
- Low-frequency rTMS significantly inhibited GBM cell proliferation and invasion in vitro.
- rTMS treatment led to substantial downregulation of Filamin A (FLNA) and Filamin C (FLNC) expression.
- In vitro, rTMS suppressed EGFR and EphA2 activation, inhibited ERK/JNK/p38 and PI3K/AKT/mTOR pathways, induced apoptosis, and downregulated MMP2/MMP9.
- In vivo, low-frequency rTMS suppressed GBM progression, correlating with FLNA and FLNC downregulation.
Conclusions:
- Low-frequency rTMS demonstrates potential as a therapeutic strategy for glioblastoma.
- The anti-cancer effects are mediated, at least in part, by the downregulation of FLNA and FLNC.
- This study provides a mechanistic basis for exploring rTMS in glioblastoma and potentially other cancers.
