期刊
MOLECULAR NEUROBIOLOGY
卷 59, 期 2, 页码 1262-1272出版社
SPRINGER
DOI: 10.1007/s12035-021-02674-6
关键词
Glioblastoma; Biochanin A; AMPK; Autophagy; Chemosensitivity; Molecular docking
资金
- National Natural Science Foundation of China [81960541/82060455]
- Natural Science Foundation of Gansu Province [20JR10RA741/21JR7RA426/2 1JR7RA420]
- Key Lab of Neurology of Gansu Province [20JR10RA766]
- Fundamental Research Funds for the Central University [lzujbky-2021-kb33]
- Lanzhou Science and Technology Bureau Project [2021-RC-97]
- Cuiying Science and Technology fund [CYXZ-01]
- Cuiying Graduate Supervisor Applicant Training Program [201803]
- Lanzhou University Second Hospital [YJSBD-13]
The study found that BCA can effectively enhance sensitivity of GBM to TMZ by inhibiting autophagy, mediated through interaction with AMPK residues. This discovery sheds new light on the potential therapeutic role of BCA in sensitizing chemoresistant GBM to TMZ.
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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