Open AccessAntitumor effects of duvelisib on Epstein–Barr virus‐associated lymphoma cells
Author(s) -
Kawada Junichi,
Ando Shotaro,
Torii Yuka,
Watanabe Takahiro,
Sato Yoshitaka,
Ito Yoshinori,
Kimura Hiroshi
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1311
Subject(s) - lymphoma , lytic cycle , cancer research , cell culture , epstein–barr virus , cell cycle checkpoint , virus , protein kinase b , cell cycle , medicine , signal transduction , biology , immunology , cancer , microbiology and biotechnology , genetics
Abstract Epstein–Barr virus ( EBV ) is a ubiquitous oncogenic virus that is associated with B cell lymphomas, including Burkitt lymphoma and Hodgkin lymphoma. Previous studies have shown that the phosphatidylinositol 3‐kinase ( PI 3K)/Akt pathway is activated in EBV ‐associated lymphomas and can be a novel therapeutic target. An oral dual inhibitor of PI 3K γ and PI 3K δ , duvelisib, is in clinical trials for the treatment of lymphoid malignancies. In this study, we evaluated how duvelisib affects the activity of the PI 3K/Akt signaling pathway and if it has antitumor effects in EBV ‐associated lymphoma cell lines. We found that the PI 3K/Akt signaling pathway was activated in most of the B and T cell lymphoma cell lines tested. Additionally, duvelisib treatment inhibited cellular growth in the tested cell lines. Overall, B cell lines were more susceptible to duvelisib than T and NK cell lines in vitro regardless of EBV infection. However, the additional influence of duvelisib on the tumor microenvironment was not assessed. Duvelisib treatment induced both apoptosis and cell cycle arrest in EBV ‐positive and ‐negative B cell lines, but not in T cell lines. Furthermore, duvelisib treatment reduced the expression of EBV lytic genes ( BZLF 1 and gp350/220) in EBV ‐positive B cell lines, suggesting that duvelisib suppresses the lytic cycle of EBV induced by B cell receptor signaling. However, duvelisib did not induce a remarkable change in the expression of EBV latent genes. These results may indicate that there is therapeutic potential for duvelisib administration in the treatment of EBV ‐associated B cell lymphomas and other B cell malignancies.