Down-regulation of intracellular reactive oxygen species attenuates P-glycoprotein-associated chemoresistance in Epstein-Barr virus-positive NK/T-cell lymphoma

American Journal of Translational Research

Keon-Il Im¹  Yunejin Song²  Young-Sun Nam³  Nayoun Kim⁴ 

[1] Department of Biomedicine and Health Sciences, The Catholic University of Korea, College of Medicine, Korea;Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Marys Hospital, The Catholic University of Korea, College of Medicine, Seoul, Korea;Institute for Translational Research and Molecular Imaging, The Catholic University of Korea, College of Medicine, Korea;Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease (CRCID), Catholic Blood and Marrow Transplantation Center, Seoul St. Marys Hospital, The Catholic University of Korea, College of Medicine, Seoul, Korea

关键词: Epstein-Barr virus (EBV);    extranodal NK/T-cell lymphoma (ENKTCL);    reactive oxygen species (ROS);    multi-drug resistance (MDR);    P-glycoprotein (P-gp);   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Epstein-Barr virus (EBV)-positive extranodal NK/T-cell lymphoma is a rare and highly aggressive disease with a poor prognosis and strong resistance to anti-cancer drugs. Reactive oxygen species (ROS) are closely related to tumorigenesis and P-glycoprotein (P-gp) is highly expressed in various cancers. However, the exact relationship between ROS and P-gp in EBV-positive lymphoma remains unclear. In this study, we demonstrated that EBV latent infection induced intracellular ROS production and increased ROS levels triggered elevated P-gp expression, which resulted in strong resistance to existing anti-cancer drugs in EBV-positive lymphoma cell lines and in patients’ tissue samples. We also verified that regulation of intracellular ROS reduced P-gp expression and function via inhibition of STAT1 phosphorylation. These results indicate that treatment with a ROS scavenger is a potential therapeutic strategy to overcome resistance to anti-cancer drugs by downregulating the expression of P-gp in EBV-positive NK/T-cell lymphoma.

【 授权许可】

CC BY-NC