謝逸憲HSIEH,YI-HSIEN賴怡安LAI, YI-ANYI-ANLAI醫學研究所碩士班2026-10-292026-07-3020262026-07-13https://handle.ncl.edu.tw/11296/68vk4yhttps://scholars.csmu.edu.tw/handle/123456789/36777神經膠質母細胞瘤 (Glioblastoma multiforme, GBM) 是成人最常見且惡性程度極高的原發性腦瘤，目前臨床治療多採用手術切除與放化療，但因復發率高且抗藥性強使得臨床治療成效不彰，導致疾病的預後極差，因此發展新的治療策略為臨床上的迫切需求。氧化白藜蘆醇 (Oxyresveratrol, OxyR) 是存在於植物中的天然多酚類化合物，過去研究指出其具有抗氧化與抗腫瘤潛力，但其在GBM中的抗癌作用機制尚未明確。本研究發現 OxyR 能顯著抑制 GBM8401、M059K 與 U-251 MG 細胞株及神經膠質母細胞瘤幹細胞 (Glioblastoma stem cells, GSCs) 之細胞生長、細胞移動與侵襲能力。在分子機制層面，OxyR 可提升 FBXW7 表現量、促進 ADAM9 蛋白質降解，活化 p38 訊息傳遞路徑及降低幹細胞標誌的表現。此外，OxyR 與臨床化療藥物替莫唑胺 (Temozolomide, TMZ) 合併使用對 GBM 細胞的生長與遷移能力具有更顯著的抑制效果。綜合上述結果，OxyR 可透過調控 FBXW7/ADAM9 及 p38 訊息傳遞路徑抑制 GBM 惡性進展，顯示其具有 GBM 輔助治療用藥之潛力。Glioblastoma multiforme (GBM) is the most common and highly aggressive primary brain tumor in adults. Current standard treatment consists of surgical resection followed by radiotherapy and chemotherapy. However, the high recurrence rate and therapeutic resistance of GBM result in poor clinical outcomes and an unfavorable prognosis. Therefore, the development of novel therapeutic strategies remains an urgent clinical need. Oxyresveratrol (OxyR), a naturally occurring polyphenolic compound found in plants, has been reported to possess antioxidant and antitumor properties. Nevertheless, its antitumor mechanisms in GBM remain largely unclear. In this study, we demonstrated that OxyR significantly inhibited cell proliferation, migration, and invasion in GBM8401, M059K, and U-251 MG cell lines, as well as in glioblastoma stem cells (GSCs). Mechanistically, OxyR upregulated the expression of FBXW7, promoted ADAM9 protein degradation, activated the p38 signaling pathway, and reduced the expression of stemness-associated markers. Furthermore, combined treatment with OxyR and the clinical chemotherapeutic agent temozolomide (TMZ) exerted greater inhibitory effects on GBM cell proliferation and migration than either treatment alone. Collectively, these findings demonstrate that OxyR suppresses the malignant progression of GBM through modulation of the FBXW7/ADAM9 axis and the p38 signaling pathway, highlighting its potential as a promising adjuvant therapeutic agent for GBM.神經膠質母細胞瘤氧化白藜蘆醇ADAM9FBXW7Glioblastoma multiformeOxyresveratrolthesis