Citation: Yuanyuan Zeng, Fang Liu, Jun Wang, Bianfei Shao, Tao He, Zhongzheng Xiang, Yan Wang, Shunyao Zhu, Tian Yang, Siting Yu, Changyang Gong, Lei Liu. Fisetin micelles precisely exhibit a radiosensitization effect by inhibiting PDGFRβ/STAT1/STAT3/Bcl-2 signaling pathway in tumor[J]. Chinese Chemical Letters, ;2025, 36(2): 109734. doi: 10.1016/j.cclet.2024.109734 shu

Fisetin micelles precisely exhibit a radiosensitization effect by inhibiting PDGFRβ/STAT1/STAT3/Bcl-2 signaling pathway in tumor

Yuanyuan Zeng ^{a, 1} ,
Fang Liu ^{b, 1} ,
Jun Wang ^{a, 1} ,
Bianfei Shao ^c ,
Tao He ^d ,
Zhongzheng Xiang ^a ,
Yan Wang ^e ,
Shunyao Zhu ^f ,
Tian Yang ^a ,
Siting Yu ^a ,
Changyang Gong ^d ,
Lei Liu ^{a, *,}

a.
Department of Radiation Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
b.
Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450000, China
c.
Chongqing Key Laboratory of translational Research for Cancer Metastasis and individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
d.
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
e.
Department of Pharmacy, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, Wuhu 241004, China
f.
Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China

liuleihx@gmail.com

Received Date: 16 January 2024
Revised Date: 22 February 2024
Accepted Date: 25 February 2024
Available Online: 8 March 2024

Figures(4)

It is of great significance to find safe and effective radiosensitizers. A primary investigation has been made on fisetin’s modification of radiation effect, but its radiosensitization and related mechanisms still need to be deeply clarified. Furthermore, fisetin with high hydrophobicity is difficult to dissolve in water, severely limiting its research and application. In this study, we fabricated a safe and soluble radiosensitizer fisetin micelle for precisely enhancing radiotherapy by inhibiting platelet-derived growth factor receptor-β (PDGFRβ)/signal transducer and activator of transcription 1 (STAT1)/signal transducer and activator of transcription 3 (STAT3)/B cell lymphoma 2 (Bcl-2) signaling pathway in the tumor. Systematic and detailed studies were performed to verify its radiosensitization effect in vitro and in vivo. On the cellular level, fisetin micelles selectively increased the radiosensitivity of tumor cells (CT26 and 4T1 cells) and had little effect on the sensitivity of normal mouse cells (L929 cells) to radiation. In the mouse models of colon and breast cancers, fisetin micelles showed an efficient radiosensitization capacity without apparent toxicity. Additionally, we first found that fisetin micelles played a radiotherapy sensitization role by inhibiting the PDGFRβ/STAT1/STAT3/Bcl-2 pathway activity. In general, this work not only confirmed that fisetin micelles precisely exhibit a radiosensitization effect in vitro and in vivo, but also profoundly explored its mechanisms underlying, to provide a theoretical and experimental basis for the clinical application of fisetin micelles.
- Fisetin,
- Polymetric micelles,
- Radiotherapy,
- Radiosensitizer,
- Platelet-derived growth factor receptor-β
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