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IL-10 contributes to gemcitabine resistance in extranodal NK/T-cell lymphoma cells via ABCC4

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Summary

Background Chemotherapy resistance is a main reason for treatment failure in extranodal NK/T-cell lymphoma (ENKTL). Interleukin-10 (IL-10) is closely related to the occurrence and prognosis of ENKTL. We intended to study the role and molecular mechanism of IL-10 in ENKTL resistance. Methods Fifty serum samples were collected from patients with a histologically proven diagnosis of ENKTL. Fifty healthy volunteers were enrolled as a control group. The level of serum IL-10 was detected by ELISA. The NK/T-cell lymphoma cell lines YT and NK-92 were divided into the control group (untreated), IL-10 group (treated with IL-10), IL-10 + GEM group (treated with IL-10 and gemcitabine simultaneously) and GEM group (treated with gemcitabine). A CCK8 assay and flow cytometry were employed to detect the effects of IL-10 on each group. Western blotting was applied to detect the expression of ABC membrane transporter family proteins and signaling pathway proteins in each group. Results Serum IL-10 levels were higher in ENKTL patients as well asin patients with ineffective treatment. The IC50 value for gemcitabine in YT and NK-92 cells increased significantly in the presence of IL-10. The effects of gemcitabine resulting in cell killing, cell cycle arrest, and apoptosis promotion were also weakened by IL-10. The expression of ABCC4, STAT1, p-STAT1, Tyk2 and p-Tyk2 was significantly increased by IL-10. Conclusion Our results indicate that IL-10 contributes to the resistance of ENKTL cells via ABCC4 and that IL-10 regulates the JAK/STAT signaling pathway in YT and NK-92 cells.

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The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Funding

This research was supported by the National Natural Science Foundation of China (8157010926).

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Authors and Affiliations

  1. Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, China

    Jia Huo

  2. Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, China

    Lijun Fu

  3. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, Henan, 450000, China

    Mengyuan Jin, Zhaoming Li & Mingzhi Zhang

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  1. Jia Huo
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  5. Mingzhi Zhang
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Contributions

J. H. and L. F. were involved in the conception and design of this study. J. H., L. F., and M. J. performed the data analysis and interpreted the results. J. H. and M. J. prepared the first draft of the manuscript. Z. L. and M. Z. critically revised the manuscript. M. Z. supervised the study.

Corresponding author

Correspondence to Mingzhi Zhang.

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All patients and healthy volunteers signed an informed consent form, and the research was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University.

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All patients and healthy volunteers signed an informed consent form.

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The author reports no conflicts of interest in this work.

Research involving human participants and/or animals

All of the procedures performed in the study involving human participants were in accordance with the ethical standards of the relevant institutional and national research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Huo, J., Fu, L., Jin, M. et al. IL-10 contributes to gemcitabine resistance in extranodal NK/T-cell lymphoma cells via ABCC4. Invest New Drugs 40, 537–545 (2022). https://doi.org/10.1007/s10637-022-01224-8

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