Taxifolin Targets PI3K and mTOR and Inhibits Glioblastoma Multiforme
Weiqi Yao,1,2 Hongyun Gong,3 Heng Mei ,1 Lei Shi,4 Jinming Yu , 2,5 and Yu Hu 1
1 Department of Hematology, Union Hospital, Tong Ji Medical College, Hua Zhong University of Science and Technology, Wuhan,
Hubei, China
2 Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University,
Shandong Academy of Medical Science, Jinan, China
3 Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
4 Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
5 Shandong Academy of Medical Science, Jinan, China
Correspondence should be addressed to Jinming Yu; sdyujinming@163.com and Yu Hu; dr_huyu@126.com Received 14 January 2021; Accepted 31 July 2021; Published 21 August 2021 Academic Editor: Dan Zhao Copyright © 2021 Weiqi Yao et al. ,is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Glioblastoma multiforme (GBM), the most common malignant primary brain tumor, has a very poor prognosis. With increasing knowledge of tumor molecular biology, targeted therapies are becoming increasingly integral to comprehensive GBM treatment strategies. mTOR is a key downstream molecule of the PI3K/Akt signaling pathway, integrating input signals from growth factors, nutrients, and energy sources to regulate cell growth and cell proliferation through multiple cellular responses. mTOR/PI3K dualtargeted therapy has shown promise in managing various cancers. Here, we report that taxifolin, a flavanone commonly found in milk thistle, inhibited mTOR/PI3K, promoted autophagy, and suppressed lipid synthesis in GBM. In silico analysis showed that taxifolin can bind to the rapamycin binding site of mTOR and the catalytic site of PI3K (p110α). In in vitro experiments, taxifolin inhibited mTOR and PI3K activity in five different glioma cell lines. Lastly, we showed that taxifolin suppressed tumors in mice; stimulated expression of autophagy-related genes LC3B-II, Atg7, atg12, and Beclin 1; and inhibited expression of fatty acid synthesis-related genes C/EBPα, PPARc, FABP4, and FAS. Our observations suggest that taxifolin is potentially a valuable drug for treating GBM
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