Pulsed and Discontinuous Electromagnetic Field Exposure Decreases Temozolomide Resistance in Glioblastoma by Modulating the Expression of O-Methylguanine-DNA Methyltransferase, Cyclin-D1, and p53.

Abstract

Glioblastoma is a malignant and very aggressive brain tumor with a poor prognosis. Despite having chemotherapy concomitant with surgery and/or radiation therapy, the median survival of glioblastoma-affected people is less than 1 year. Temozolomide (TMZ) is a chemotherapeutic used as a first line treatment of glioblastoma. Several studies have reported that resistance to TMZ due to overexpression of O-methylguanine-DNA methyltransferase (MGMT) is the main reason for treatment failure. Several studies described that pulsed-electromagnetic field (EMF) exposure could induce cell death and influence gene expression. In this study the authors assessed the effects of EMF (50 Hz, 70 G) on cytotoxicity, cell migration, gene expression, and protein levels in TMZ-treated T98 and A172 cell lines. In this study, the authors show that treatment with a combination of TMZ and EMF enhanced cell death and decreased the migration potential of T98 and A172 cells. The authors also observed overexpression of the p53 gene and downregulation of cyclin-D1 protein in comparison to controls. In addition, T98 cells expressed the MGMT protein following treatment, while the A172 cells did not express MGMT. Their data indicate that EMF exposure improved the cytotoxicity of TMZ on T98 and A172 cells and could partially affect resistance to TMZ in T98 cells.

AI evidence extraction

Main findings

In TMZ-treated T98 and A172 glioblastoma cell lines, exposure to EMF (50 Hz, 70 G) in combination with TMZ enhanced cell death and decreased migration compared with controls. The study reports p53 gene overexpression and cyclin-D1 protein downregulation versus controls; MGMT protein expression was observed in T98 after treatment but not in A172. The authors conclude EMF exposure improved TMZ cytotoxicity in both lines and could partially affect TMZ resistance in T98 cells.

Outcomes measured

• Cytotoxicity/cell death
• Cell migration
• Gene expression (p53)
• Protein expression (cyclin-D1, MGMT)
• Temozolomide resistance (MGMT-related)

Limitations

• In vitro study in glioblastoma cell lines (T98, A172); no human/clinical outcomes reported
• Exposure duration and detailed exposure protocol not provided in the abstract
• No sample sizes/replicates reported in the abstract

{
    "study_type": "in_vitro",
    "exposure": {
        "band": "ELF",
        "source": null,
        "frequency_mhz": 0.05000000000000000277555756156289135105907917022705078125,
        "sar_wkg": null,
        "duration": null
    },
    "population": null,
    "sample_size": null,
    "outcomes": [
        "Cytotoxicity/cell death",
        "Cell migration",
        "Gene expression (p53)",
        "Protein expression (cyclin-D1, MGMT)",
        "Temozolomide resistance (MGMT-related)"
    ],
    "main_findings": "In TMZ-treated T98 and A172 glioblastoma cell lines, exposure to EMF (50 Hz, 70 G) in combination with TMZ enhanced cell death and decreased migration compared with controls. The study reports p53 gene overexpression and cyclin-D1 protein downregulation versus controls; MGMT protein expression was observed in T98 after treatment but not in A172. The authors conclude EMF exposure improved TMZ cytotoxicity in both lines and could partially affect TMZ resistance in T98 cells.",
    "effect_direction": "benefit",
    "limitations": [
        "In vitro study in glioblastoma cell lines (T98, A172); no human/clinical outcomes reported",
        "Exposure duration and detailed exposure protocol not provided in the abstract",
        "No sample sizes/replicates reported in the abstract"
    ],
    "evidence_strength": "low",
    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "glioblastoma",
        "temozolomide",
        "pulsed electromagnetic field",
        "ELF-EMF",
        "50 Hz",
        "70 G",
        "MGMT",
        "p53",
        "cyclin-D1",
        "cell migration",
        "cytotoxicity",
        "drug resistance"
    ],
    "suggested_hubs": []
}

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