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Integrating network pharmacology and experimental validation to explore the potential mechanism by which resveratrol acts on osimertinib resistance in lung cancer

  • Authors:
    • Xin Yu
    • Yuan Yao
    • Haiwen Zhou
    • Jintao Zhu
    • Nini Zhang
    • Shuliu Sang
    • Hailun Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, Traditional Chinese Medical Hospital of Zhuji, Zhuji, Zhejiang 311800, P.R. China, Department of TCM, Shimen Er Lu Community Health Service Center of Jing'an District, Shanghai 200041, P.R. China, Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China
    Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 192
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    Published online on: February 20, 2025
       https://doi.org/10.3892/ol.2025.14938
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Abstract

Globally, osimertinib resistance has been a long‑term challenge. Resveratrol, a naturally occurring polyphenolic compound found in various plants, has the potential to modulate multidrug resistance mechanisms. However, the specific role of resveratrol in delaying osimertinib resistance in lung cancer is still unclear. The present study aimed to investigate the therapeutic effects and underlying mechanisms of resveratrol in delaying osimertinib resistance. Accordingly, the corresponding targets of resveratrol were screened through the Traditional Chinese Medicine Systems Pharmacology database. Similarly, the corresponding targets for osimertinib resistance were mined from the GeneCards database. A protein‑protein interaction network was subsequently constructed to pinpoint key hub genes that resveratrol may target to delay resistance. Molecular docking analysis was then employed to assess the binding energy between the predicted key targets and resveratrol. Finally, in vitro experiments were performed to validate the results. Ultimately, 13 potential therapeutic targets of resveratrol related to delaying osimertinib resistance were identified. Kyoto Encyclopedia of Genes and Genomes analysis suggested that the effects of resveratrol may be associated with the apoptotic pathway. Molecular docking revealed that resveratrol has good binding affinities with MCL1 and BCL2L11. In vitro experiments confirmed that resveratrol inhibited the proliferation of osimertinib‑resistant cells and upregulated the expression of BCL2L11. In conclusion, resveratrol may promote apoptosis by targeting BCL2L11 to delay osimertinib resistance.
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Copy and paste a formatted citation
Spandidos Publications style
Yu X, Yao Y, Zhou H, Zhu J, Zhang N, Sang S and Zhou H: Integrating network pharmacology and experimental validation to explore the potential mechanism by which resveratrol acts on osimertinib resistance in lung cancer. Oncol Lett 29: 192, 2025.
APA
Yu, X., Yao, Y., Zhou, H., Zhu, J., Zhang, N., Sang, S., & Zhou, H. (2025). Integrating network pharmacology and experimental validation to explore the potential mechanism by which resveratrol acts on osimertinib resistance in lung cancer. Oncology Letters, 29, 192. https://doi.org/10.3892/ol.2025.14938
MLA
Yu, X., Yao, Y., Zhou, H., Zhu, J., Zhang, N., Sang, S., Zhou, H."Integrating network pharmacology and experimental validation to explore the potential mechanism by which resveratrol acts on osimertinib resistance in lung cancer". Oncology Letters 29.4 (2025): 192.
Chicago
Yu, X., Yao, Y., Zhou, H., Zhu, J., Zhang, N., Sang, S., Zhou, H."Integrating network pharmacology and experimental validation to explore the potential mechanism by which resveratrol acts on osimertinib resistance in lung cancer". Oncology Letters 29, no. 4 (2025): 192. https://doi.org/10.3892/ol.2025.14938
Copy and paste a formatted citation
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Spandidos Publications style
Yu X, Yao Y, Zhou H, Zhu J, Zhang N, Sang S and Zhou H: Integrating network pharmacology and experimental validation to explore the potential mechanism by which resveratrol acts on osimertinib resistance in lung cancer. Oncol Lett 29: 192, 2025.
APA
Yu, X., Yao, Y., Zhou, H., Zhu, J., Zhang, N., Sang, S., & Zhou, H. (2025). Integrating network pharmacology and experimental validation to explore the potential mechanism by which resveratrol acts on osimertinib resistance in lung cancer. Oncology Letters, 29, 192. https://doi.org/10.3892/ol.2025.14938
MLA
Yu, X., Yao, Y., Zhou, H., Zhu, J., Zhang, N., Sang, S., Zhou, H."Integrating network pharmacology and experimental validation to explore the potential mechanism by which resveratrol acts on osimertinib resistance in lung cancer". Oncology Letters 29.4 (2025): 192.
Chicago
Yu, X., Yao, Y., Zhou, H., Zhu, J., Zhang, N., Sang, S., Zhou, H."Integrating network pharmacology and experimental validation to explore the potential mechanism by which resveratrol acts on osimertinib resistance in lung cancer". Oncology Letters 29, no. 4 (2025): 192. https://doi.org/10.3892/ol.2025.14938
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