Enhancing radiotherapy in triple-negative breast cancer with hesperetin-induced ferroptosis via AURKA targeting nanocomposites

被引:0
|
作者
Guo, Yang [1 ]
Wang, Huan [2 ]
Wang, Xinlei [3 ]
Chen, Keyan [4 ]
Feng, Liang [1 ]
机构
[1] First Hosp China Med Univ, Dept Breast Surg, 155 Nanjingbei St, Shenyang 110001, Liaoning, Peoples R China
[2] China Med Univ, Dept Gynecol, Affiliated Hosp 1, Shenyang 110001, Liaoning, Peoples R China
[3] First Hosp China Med Univ, Dept Intervent Therapy, Shenyang 110001, Liaoning, Peoples R China
[4] China Med Univ, Lab Anim Sci, 77,Puhe Rd, Shenyang 110122, Liaoning, Peoples R China
关键词
Triple-negative breast cancer; Ferroptosis; Hesperetin; AURKA; Redox homeostasis; Radiotherapy efficacy; POTENTIAL ROLE; HESPERIDIN; THERAPY; IRON;
D O I
10.1186/s12951-024-02987-3
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Triple-negative breast cancer (TNBC) is an aggressive cancer type that lacks targeted treatment options. Ferroptosis, a novel therapeutic strategy, induces cell death by disrupting the oxidative-reductive balance. Hesperetin, a potential TNBC therapeutic drug, has unidentified regulatory targets. The objective of this study was to explore the potential targets of hesperetin in TNBC and investigate whether the nanocomposites carrier hesperetin-loaded ferroptosis-inducing nanocomposites (HFPN), which activates ferroptosis, can enhance the anti-tumor efficacy of hesperetin. Bioinformatics methods were employed to screen hesperetin targets in TNBC, and a molecular docking model between hesperetin and the core target aurora kinase A (AURKA) was successfully constructed. The stability and anti-tumor activity of HFPN were validated in cell and mouse models, including tumor suppression and increased radiation sensitivity. These results suggest that HFPN can regulate the core target AURKA in TNBC, disrupt tumor oxidative-reductive balance, promote ferroptosis in tumor cells, and ultimately enhance the effectiveness of radiation therapy for TNBC.
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页数:21
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