ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Astragalus small molecules protect BMSCs from radiation-induced bystander effect and enhance lung cancer radiosensitivity via the primary cilium/TGFβR1/Smad3 pathway
Zhiming Miao
Mengyuan Wu
Sichao Dai
Xin Wang
Yang Yang Li
Fuxian Liu
Zhiwei Liu
Liying Zhang
Yongqi Liu
Gansu University of Chinese Medicine, Lanzhou, China
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Abstract
Background: Radiotherapy is crucial for lung cancer treatment, but side effects and decreased radiosensitivity are challenging issues. TGFβR1 can induce the radiation-induced bystander effect (RIBE) via primary cilia, yet the underlying mechanism is unclear. Traditional Chinese medicine (TCM), especially astragalus, shows promise in protecting against RIBE, but its protective mechanism is unknown. This study aimed to explore the molecular mechanisms of TGFβR1-induced RIBE through primary cilia and the therapeutic effects of astragalus small molecules. Methods: A co-culture model of A549 cells and bone marrow mesenchymal stem cells (BMSCs) was established. Network pharmacology identified key proteins in radiation-induced DNA damage repair in BMSCs. The role of the primary cilium/TGFβR1 pathway was investigated using immunofluorescence and Western blot. Molecular docking screened effective astragalus small molecules targeting this pathway. The effects of these small molecules on RIBE were studied using CCK-8, colony formation, apoptosis, cell cycle, immunofluorescence, and Western blot assays. Results: Bioinformatics analysis identified IFT88 as a core differentially expressed gene. In the co-culture model, BMSCs were inhibited by RIBE after A549 irradiation. TGFβR1, IFT88, and RAD51 were abnormally activated in adjacent BMSCs post-irradiation. Knockdown of IFT88 significantly reduced TGFβR1 and RAD51 expression. Molecular docking identified vanillic acid and 3-hydroxy-9,10-dimethoxy rosewood from astragalus. These compounds, alone or combined with radiation, decreased TGFβR1 and RAD51 expression and primary cilium number in paracellular and lung cancer cells, but did not affect TGFβR1 expression levels. Conclusion: Primary cilia are crucial for repairing radiation-induced DNA damage in adjacent BMSCs and enhancing lung cancer radiosensitivity. Astragalus small molecules vanillic acid and rosewood can regulate BMSC DNA damage via the TGFβR1/primary cilium pathway.
Summary
Keywords
Bystander Effect, DNA Damage, primary cilia, Rosewood, TGFβR1, Vanillic Acid
Received
25 October 2025
Accepted
15 January 2026
Copyright
© 2026 Miao, Wu, Dai, Wang, Li, Liu, Liu, Zhang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Liying Zhang; Yongqi Liu
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