Biochanin A Sensitizes Glioblastoma to Temozolomide by Inhibiting Autophagy
Biochanin A Sensitizes Glioblastoma to Temozolomide by Inhibiting Autophagy
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DOI：
10.1007/s12035-021-02674-6
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发表时间：
2022-01-04
影响因子：
5.1
通讯作者：
Pan, Yawen
中科院分区：
文献类型：
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作者：
Dong, Qiang;Wang, Degui;Pan, Yawen
替莫唑胺（TMZ）化疗耐药是胶质母细胞瘤（GBM）患者治疗失败的主要原因。在本研究中，我们研究了鹰嘴豆芽素A（BCA）的TMZ在GBM中的有效增敏剂。我们观察到BCA在体外和体内显著增强细胞对TMZ的敏感性。从机制上讲，BCA的特异性化学增敏作用是由自噬抑制介导的。此外，通过进行分子对接分析，我们证明了BCA与AMPK残基相互作用，并通过调节AMPK/ULK 1通路来损害自噬。这些结果表明，BCA是一种潜在的治疗剂，使GBM对TMZ敏感，并为化疗耐药GBM的治疗潜力提供了新的见解。
Resistance to temozolomide (TMZ) chemotherapy is the main reason for treatment failure in patients with glioblastoma (GBM). In the present study, we investigated biochanin A (BCA) a potent sensitizer of TMZ in GBM. We observed that BCA significantly enhanced cell sensitivity to TMZ in vitro and in vivo. Mechanistically, the specific chemosensitizing effect of BCA is mediated by autophagy inhibition. Moreover, by performing a molecular docking analysis, we demonstrated that BCA interacts with AMPK residues and impairs autophagy by regulating the AMPK/ULK1 pathway. These results suggest that BCA is a potential therapeutic agent that sensitizes GBM to TMZ and provide new insight into its therapeutic potential in chemoresistant GBM.