替莫唑胺
癌症研究
自噬
PI3K/AKT/mTOR通路
药理学
胶质瘤
胶质母细胞瘤
化学
蛋白激酶B
细胞凋亡
医学
活力测定
作者
Qiang Dong,Degui Wang,Lanlan Li,Jie Wang,Qiao Li,Lei Duan,Hang Yin,Xiaoqing Wang,Yang Liu,Guoqiang Yuan,Yawen Pan
标识
DOI:10.1007/s12035-021-02674-6
摘要
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.
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