Abstract: Objective To investigate the effects of bortezomib and lenalidomide on the induction of cell apoptosis in natural killer/T-cell lymphoma(NK/TCL) cell lines. Methods Trypan blue exclusion test was used to account living cells.Flow cytometry was applied to detect cell apoptosis and contents of cellular DNA for analysis of cell cycle distribution.The apoptotic cells were quantified by dual labeling of recombinant annexin V and propidium iodide. Results The cytotoxic effects of bortezomib on SNK-1,SNK-6 and SNT-8 were observed.Bortezomib at clinical therapeutic concentrations significantly reduced the cells survival by inducing cell apoptosis in NK/TCL cell lines.The percentages of survival cells were (47.2±3.5)%,(33.5±3.9)%,(52.1±4.3)% for SNK-1,SNK-6,and SNT-8,respectively,after bortezomib(30 nmol/L) treatment for 24 hours(P＜0.01 as compared with control).The IC 50 of bortezomib for SNK-1,SNK-6,and SNT-8 were 19.5,12.7,and 20.7 nmol/L,respectively.By flow cytometry analysis,we found that 24 hours exposure to bortezomib significant induced apoptosis with (47.0±4.2)% for SNK1(30 nmol/L),43.0±3.8% for SNK6(10 nmol/L),and (53.0±4.1)% for SNK-8 (30 nmol/L).Lenalidomide showed no significant effect on cell survival,cell proliferation and distribution of cell cycle.Lenalidomide in combination with bortezomib showed no synergistic effect on inducing cell apoptosis. Conclusion Bortezomib is a powerful agent in inducing NK/TCL cells apoptosis.It is a potential therapeutic agent in NK/TCL treatment.Lenalidomide showed no significant effect on NK/TCL cells in culture;moreover,it showed no synergistic effect with bortezomib on inducing cell apoptosis.Whether lenalidomide has effect on NK/TCL in vivo should be further studied.