{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:28:30Z","timestamp":1788881310943,"version":"build-2803163510"},"reference-count":33,"publisher":"Georg Thieme Verlag KG","issue":"09","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Glioblastoma multiforme continues to pose a major therapeutic challenge due to its high level of treatment resistance and poor prognosis. Temozolomide is a standard chemotherapeutic agent, but resistance significantly limits its clinical efficacy.<\/jats:p>\n                  <jats:p>This study investigated the potential of resveratrol to overcome temozolomide resistance in glioblastoma cells by examining its effects on molecular mechanisms of drug resistance.<\/jats:p>\n                  <jats:p>Human glioblastoma cell lines U251 and temozolomide-resistant U251\/temozolomide were utilized. Cellular viability was assessed using the MTT assay. Molecular mechanisms were evaluated through qRT-PCR, Western blotting, Rhodamine 123 accumulation, and apoptosis detection techniques. The study examined alterations in P-glycoprotein (P-gp) expression, mitogen-activated protein kinase\/ERK signaling pathway, and apoptotic markers.<\/jats:p>\n                  <jats:p>Resveratrol significantly reduced the temozolomide resistance of U251\/temozolomide cells, lowering the IC50 from 91.89 to 24.5 \u00b5M. Combined treatment demonstrated enhanced apoptotic cell death, significant downregulation of P-gp expression and activity, suppression of the mitogen-activated protein kinase\/ERK signaling pathway, and upregulation of tumor suppressor miR-647.<\/jats:p>\n                  <jats:p>Resveratrol demonstrates potential as an adjuvant therapy by sensitizing temozolomide-resistant glioblastoma cells through multiple molecular mechanisms. It offers a promising approach to overcome chemotherapeutic resistance.<\/jats:p>","DOI":"10.1055\/a-2698-0203","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T23:37:43Z","timestamp":1763509063000},"page":"379-385","source":"Crossref","is-referenced-by-count":1,"title":["Resveratrol Sensitizes Temozolomide-Resistant Glioblastoma Cells Through Mitogen-Activated Protein Kinase Pathway Inhibition and P-Glycoprotein Modulation"],"prefix":"10.1055","volume":"75","author":[{"given":"Maede","family":"Rezaie","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Nasehi","sequence":"additional","affiliation":[{"name":"Cognitive and Neuroscience Research Center, Amir-Almomenin Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariush","family":"Shanehbandi","sequence":"additional","affiliation":[{"name":"Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Valizadeh","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4220-1527","authenticated-orcid":false,"given":"Bahman","family":"Yousefi","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, 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