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    標題: Flunarizine, a drug approved for treating migraine and vertigo, exhibits cytotoxicity in GBM cells
    作者: Chen, Shih-Han
    Chao, Chun-Nun
    Chen, San-Yuan
    Lin, Han-Pei
    Huang, Hsin-Yi
    Fang, Chiung-Yao
    貢獻者: Ditmanson Med Fdn, Dept Neurosurg, Chiayi Christian Hosp
    Ditmanson Med Fdn, Dept Pediat, Chiayi Christian Hosp
    Asia Univ, Dept Med Lab Sci & Biotechnol
    Ditmanson Med Fdn, Dept Chinese Med, Chiayi Christian Hosp
    Chia Nan Univ Pharm & Sci, Dept Sports Management
    Ditmanson Med Fdn, Chiayi Christian Hosp, Dept Med Res
    關鍵字: Flunarizine
    Synergistic effect
    GBM
    Apoptosis
    日期: 2021
    上傳時間: 2023-11-11 11:58:53 (UTC+8)
    出版者: ELSEVIER
    摘要: Glioblastoma multiforme (GBM) is the most aggressive brain tumor with a poor prognosis. The current treatment regimen, including surgical resection, radiation, and temozolomide (TMZ) chemotherapy, is still not curative. Therefore, there is an emerging need to develop a drug to treat GBM or synergistic enhance TMZ effect on GBM cells. Flunarizine (FLN), a drug approved for treating migraine and vertigo, was analyzed for its cytotoxicity and synergistic effect with TMZ on GBM cells in this study. Cell proliferation, clonogenic assay, flow cytometry, and Western blotting were used to determine the effects of FLN on three GBM cells, U-87 MG, LN-229, and U-118 MG cells. We found that FLN induced GBM cell death. FLN also interfered with U-87 MG cell cycle progression. Flow cytometric analysis showed an increase of apoptotic cells after FLN treatment. Caspase 9, caspase 3, and Poly (ADP-ribose) polymerase (PARP) activation were involved in apoptosis induction in U-87 MG and LN-229, suggesting the possible involvement of an intrinsic apoptotic pathway. We found that FLN treatment inhibited Akt pathway activation in U-87 MG cells, and synergistically increased the cytotoxicity of three GBM cells when combined with TMZ treatment. In conclusion, our current data suggested that FLN inhibited cell viability by inducing apoptosis. FLN inhibited Akt activation and enhanced the sensitivity of GBM cells to TMZ. These findings may provide important information regarding the application of FLN in GBM treatment in the future.
    關聯: EUR J PHARMACOL, v.892, 173756
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