ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Dasatinib and quercetin mitigate radiation-induced lung injury by eliminating senescent cells in a rat model
Jing Liu 1
Xue Ren 2
Hengjiao Wang 2
Defu Yang 2
Ying Yan 2
Ying Xu 2
1. Dalian Medical University Graduate School, Dalian, China
2. General Hospital of Northern Theatre Command, Shenyang, China
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Abstract
Background: Radiation-induced lung injury (RILI) is a major dose-limiting toxicity in thoracic radiotherapy, and accumulating evidence implicates radiation-induced cellular senescence in its pathogenesis. This study aimed to investigate whether combination therapy with dasatinib and quercetin (DQ) could mitigate RILI by reducing senescent cell burden. Methods: A rat model of RILI was established using a single 30 Gy irradiation to the right lung. Pulmonary pathological changes, fibrosis, DNA damage, and cellular senescence were assessed by histology, immunofluorescence, senescence-associated β-galactosidase staining, Western blotting and immunohistochemistry. Transcriptomic profiling was performed to explore the underlying molecular mechanisms. Results: Compared with irradiation alone, DQ treatment significantly alleviated radiation-induced inflammatory cell infiltration and collagen deposition, reduced γH2AX levels, decreased senescence-associated markers p53, p21, and p16, and suppressed multiple senescence-associated secretory phenotype (SASP) factors. Transcriptomic analysis indicated that DQ-mediated effects were closely associated with activation of apoptotic pathways and modulation of p53, MAPK, PI3K-Akt and mitophagy signaling cascades. Conclusion: DQ attenuated RILI in rats, with effects consistent with the reduced radiation-induced senescent cells and suppression of senescence-associated inflammatory responses.
Summary
Keywords
cellular senescence, Dasatinib and quercetin, DNA Damage, Radiation-induced lung injury, senescence-associated secretory phenotype
Received
18 November 2025
Accepted
22 January 2026
Copyright
© 2026 Liu, Ren, Wang, Yang, Yan and Xu. 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: Ying Yan; Ying Xu
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