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

Abstract

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.

• Authors: Jia Huo, Lijun Fu, Mengyuan Jin, Zhaoming Li, Mingzhi Zhang
• Journal: Investigational new drugs (Invest New Drugs) Vol. 40 Issue 3 Pg. 537-545 (06 2022) ISSN: 1573-0646 [Electronic] United States
• PMID: 35226228 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• ABCC4 protein, human
• IL10 protein, human
• Multidrug Resistance-Associated Proteins
• Deoxycytidine
• Interleukin-10
• Gemcitabine

Topics

• Deoxycytidine (analogs & derivatives, pharmacology)
• Drug Resistance, Neoplasm
• Humans
• Interleukin-10 (metabolism, pharmacology, therapeutic use)
• Lymphoma, Extranodal NK-T-Cell (drug therapy, metabolism, pathology)
• Multidrug Resistance-Associated Proteins (metabolism)
• Gemcitabine