Bortezomib induces apoptosis in T lymphoma cells and natural killer lymphoma cells independent of Epstein-Barr virus infection

作者：Iwata Seiko; Yano Shoko; Ito Yoshinori; Ushijima Yoko; Gotoh Kensei; Kawada Jun ichi; Fujiwara Shigeyoshi; Sugimoto Koichi; Isobe Yasushi; Nishiyama Yukihiro; Kimura Hiroshi^*

来源：International Journal of Cancer, 2011, 129(9): 2263-2273.

DOI：10.1002/ijc.25873

• Epstein-Barr virus
• proteasome inhibitor
• apoptosis
• lytic infection
• NF-kappa B

Epstein-Barr virus (EBV), which infects not only B cells, but also T cells and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, the proteasome inhibitor bortezomib was reported to induce apoptosis of EBV-transformed B cells. We evaluated the killing effect of this proteasome inhibitor on EBV-associated T lymphoma cells and NK lymphoma cells. First, we found that bortezomib treatment decreased the viability of multiple T and NK cell lines. No significant difference was observed between EBV-positive and EBV-negative cell lines. The decreased viability in response to bortezomib treatment was abrogated by a pan-caspase inhibitor. The induction of apoptosis was confirmed by flow cytometric assessment of annexin V staining. Additionally, cleavage of caspases and polyadenosine diphosphate-ribose polymerase, increased expression of phosphorylated I kappa B, and decreased expression of inhibitor of apoptotic proteins were detected by immunoblotting in bortezomib-treated cell lines. We found that bortezomib induced lytic infection in EBV-positive T cell lines, although the existence of EBV did not modulate the killing effect of bortezomib. Finally, we administered bortezomib to peripheral blood mononuclear cells from five patients with EBV-associated lymphoproliferative diseases. Bortezomib had a greater killing effect on EBV-infected cells. These results indicate that bortezomib killed T or NK lymphoma cells by inducing apoptosis, regardless of the presence or absence of EBV.

• 出版日期2011-11-1