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    Study on Cantharidin Reversing the Drug-resistance of Non-small Cell Lung Cancer to DDP by Regulating the Expression of PD-L1

    Xing Jin1, Chunhui Ma2, Xiaojing Tan3, Jian Qian1, Yongbing Chen1, Dongfeng Wang4 Corresponding author

    1. 1Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, CHINA.
    2. 2Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, CHINA.
    3. 3Department of Oncology, Dong Ying People’s Hospital, Dongying, Shandong Province, CHINA.
    4. 4Department of Thoracic Surgery, Dong Ying People’s Hospital, Dongying, Shandong Province, China.

    CORRESPONDENCE

    Dongfeng Wang

    Department of Thoracic Surgery, Dong Ying People’s Hospital, Dongying, Shandong Province, China.

    dongfengwang3620@sohu.com

    Received: 06-12-2023; Accepted: 08-04-2024.

    Volume 21, Issue 1 · pp. 74–80 · PUBLISHED 2025 · DOI: 10.1177/09731296241262832

    View on Pharmacogn. Mag. original site ↗

    ABSTRACT

    Background and Purpose: Cantharidin can or cannot reverse the drug resistance of non-small cell lung cancer to cisplatin (DDP) by reducing the expression of programmed cell death ligand 1 (PD-L1). Materials and Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method was used to screen for sublethal doses of cantharidin and determine its sensitizing effect on DDP. Detect the apoptosis rate of A549/DDP cells treated with cantharidin, DDP, or the combination of cantharidin and DDP. The effects of cantharidin on the expressions of p53 and PD-L1 in the cell line were investigated. Furthermore, pifithrin-α (PFT-α) pretreatment was performed to inhibit the function of p53 and verify whether cantharidin can affect the expression of PD-L1 through p53. Results: Cantharidin significantly enhanced the sensitivity of cells to DDP and increased the apoptosis of cells induced by DDP. Cantharidin upregulated the expression of p53 in A549/DDP cells with wild-type p53 and downregulated the expression of PD-L1. Pretreatment with PFT-α inhibited the apoptosis of cells induced by the combination treatment of cantharidin and DDP. Conclusion: Cantharidin can regulate the expression of p53 and downregulate the PD-L1 in non-small cell lung cancer with wild-type p53. It may enhance the sensitivity of non-small cell lung cancer to DDP by further altering the levels of PD-L1 through the regulation of p53 expression.

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      Jin, X., Ma, C., Tan, X., Qian, J., Chen, Y., & Wang, D. (2025). Study on Cantharidin Reversing the Drug-resistance of Non-small Cell Lung Cancer to DDP by Regulating the Expression of PD-L1. Pharmacognosy Magazine, 21(1), 74–80. https://doi.org/10.1177/09731296241262832