Tumor suppressive effect of low-frequency repetitive transcranial magnetic stimulation on glioblastoma progression.

in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics by Seongmoon Jo, Sang Hee Im, Sung Hoon Kim, Dawoon Baek, Jin-Kyoung Shim, Seok-Gu Kang, Jong Hee Chang, Geneva Rose Notario, Do-Won Lee, Ahreum Baek, Sung-Rae Cho

TLDR

  • The study found that low-frequency rTMS inhibits cell proliferation and induces apoptosis in GBM models, suggesting its potential as a treatment for glioblastoma.

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.

Overview

  • The study investigated the effects of low-frequency rTMS on in vitro and in vivo glioblastoma (GBM) models to elucidate its underlying biological mechanism on GBM.
  • The study used various assays to assess the effects of rTMS on GBM models, including cell proliferation, transcriptome array analysis, and protein expression.
  • The primary objective of the study was to explore rTMS as a potential treatment for GBM and to identify its underlying biological mechanism.

Comparative Analysis & Findings

  • Low-frequency rTMS significantly inhibited cell proliferation in in vitro GBM models.
  • Transcriptome array analysis revealed a substantial downregulation of FLNA and FLNC expression after low-frequency rTMS treatment.
  • Low-frequency rTMS suppressed the activation of EGFR and EphA2, inhibited ERK/JNK/p38 and PI3K/AKT/mTOR pathways, and induced apoptosis in in vitro GBM tumor sphere models.

Implications and Future Directions

  • The study suggests that low-frequency rTMS could be a potential treatment for GBM by downregulating FLNA and FLNC expression.
  • Future studies should investigate the optimal frequency and dosing of rTMS for GBM treatment.
  • rTMS may have potential application as a therapeutic strategy for other types of cancers beyond GBM.
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