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It is associated with a poor prognosis and high recurrence rates. Although temozolomide (TMZ) remains the standard first\u2010line chemotherapy for GBM, its clinical efficacy is often limited by the development of drug resistance and toxic effects on normal tissues. Melatonin (Mel), a natural indoleamine synthesised by the pineal gland, has demonstrated synergistic anti\u2010tumour effects when combined with various chemotherapy agents in multiple studies. This study investigates the synergistic potential of Mel to enhance TMZ's therapeutic efficacy against GBM. The results demonstrate that the combination of Mel and TMZ significantly inhibits glioblastoma cell proliferation, migration, and invasion. Mechanistically, this synergistic effect is mediated through the NF\u2010\u03baB\/COX\u20102 signalling pathway. Mel enhances TMZ's anti\u2010tumour activity by inhibiting I\u03baB\u03b1 phosphorylation, suppressing NF\u2010\u03baB activation, and downregulating COX\u20102 expression. Additionally, the combination treatment induced apoptosis via activation of the Caspase\u20103 pathway. These results suggest that Mel can potentiate the therapeutic efficacy of TMZ in glioblastoma treatment, offering a promising strategy to overcome TMZ resistance while reducing its associated toxicity.<\/jats:p>","DOI":"10.1111\/jcmm.70778","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T04:14:31Z","timestamp":1755144871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Melatonin Synergises the Chemotherapeutic Effect of Temozolomide in Glioblastoma by Suppressing\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    \/\n                    <scp>COX<\/scp>\n                    \u20102 Signalling Pathways"],"prefix":"10.1111","volume":"29","author":[{"given":"Hong","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Integrated Medicine, College of Integrated Medicine Dalian Medical 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