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. 2025 Jun 16.
doi: 10.1007/s00210-025-04361-y. Online ahead of print.

Investigating the therapeutic role of anlotinib in radiation-induced lung injury

Mouqi Bai  1 , Gege Liang  2 , Ruijie Sun  3 , Yuyu Dong  1 , Cuicui Geng  2 , Bin Wang  1 , Baogang Liu  2 , Lizhe Sun  4
Affiliations

Investigating the therapeutic role of anlotinib in radiation-induced lung injury

Mouqi Bai et al. Naunyn Schmiedebergs Arch Pharmacol. .

Abstract

Radiation-induced lung injury (RILI), manifesting in its initial phase as radiation pneumonitis (RP) and progressing over time to radiation-induced pulmonary fibrosis (RIPF), represents a significant adverse consequence associated with thoracic radiation therapy. Currently, there are limited therapeutic options for RILI. Anlotinib was confirmed the efficacy of pulmonary fibrosis. Therefore, anlotinib has the potential to treat RILI. To investigate the therapeutic role of anlotinib in RILI. RILI model in mice was successfully developed for evaluating the therapeutic efficacy of anlotinib. We used network pharmacology to find six target genes and analysed the correlation between these genes and RILI-related cytokines. Molecular docking further validates the binding ability of these target genes and anlotinib. We found the importance of TGF-β in anlotinib treatment of RILI by the results of network pharmacology and correlation analysis. We then used immunohistochemistry to demonstrate that anlotinib treats RILI by lowering TGF-β. Through enrichment analysis, we obtained potential therapeutic pathways and validated them with WB. In vivo investigations demonstrated that anlotinib is able to treat RILI: Inflammation, fibrosis, and apoptosis are reduced. This result is likely to be related to the reduction of TGF-β: The therapeutic mechanism potentially involves six genes, namely, FLT1, AKT1, KDR, TGFB2, PDGFRB1, and FGFR1; these targets bind well to anlotinib; we found that the expression of most of cytokines affecting the particular processes of RILI was closely associated with the six genes, in particular TGF-β1-3; immunohistochemistry further demonstrates that anlotinib treats RILI by lowering TGF-β1-3. In addition, KEGG enrichment analysis reveals possible pathways involving in therapeutic effects, including the PI3K-Akt, MAPK, Rap1, and Ras pathway. WB showed that anlotinib treatment significantly inhibited the PI3K/Akt signalling pathway. Therefore, anlotinib has the potential for treating RILI. Our results indicated the potential targets and molecular mechanism of anlotinib against RILI.

Keywords: Anlotinib; Correlation analyses; Molecular docking; Network pharmacology; Radiation-induced lung injury; Radiation-induced pulmonary fibrosis.

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Conflict of interest statement

Declarations. Ethics approval: The reported experiments are in accordance with the standards outlined in the 8th Edition of Guide for the Care and Use of Laboratory Animals published by the National Academy of Sciences, The National Academies Press, Washington DC, USA. This study adheres to internationally accepted standards for animal research, following the 3Rs principle. The ARRIVE guidelines were employed for reporting experiments involving live animals, promoting ethical research practices. This study was approved by the Ethical Committee of Shaanxi University of Chinese Medicine, China (Approval No. SUCMDL20240424001). We uploaded the copy of the approval when uploaded our manuscript. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

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