ObjectiveTo investigate the anti-tumor effect of bortezomib on extranodal natural killer/T cell lymphoma, nasal type (ENKTL).MethodsSNK-6 cells were treated with different mass concentrations of bortezomib (0, 1, 2, 4, 5, 6 ng/mL) for 24, 48, 72 h, and different concentrations of nuclear factor-kappa B (NF-κB) signaling pathway inhibitor BAY11-7082 (0, 1, 2, 2.5, 5, 10, 20 μmol/L) for 24 h respectively, then the cell viability was measured by CCK8 kit and the half inhibitory concentration (IC50) was calculated. SNK-6 cells were treated with 30μmol/L Z-VAD-FMK (Pan-caspase inhibitor)+3ng/mL bortezomib, and 5, 10 μmol/L BAY11-7082+3 ng/mL bortezomib for 24 h respectively, then the cell viability was measured by CCK8 kit. After treatment of SNK-6 cells with different mass concentrations of bortezomib for 24 h, apoptosis was detected by AnnexinⅤ/PI flow cytometry; the expression of apoptosis-related protein Caspase-3, poly ADP-ribose polymerase (PARP) and Bcl-2 and NF-κB signaling pathway key proteins P65 and P100/P52 were detected by Western blot.ResultsBortezomib inhibited the proliferation of SNK-6 cells in a dose-dependent manner (P<0 .05), and ic50﹝(2.87±0.06) ng/mL﹞at 24 h was lower than that at 48 h and 72 h (P<0 .05). bay11-7082 also inhibited the proliferation of snk-6 cells with an ic50= (9.73±0.36) μmol/L at 24 h. The combination treatment indicated that Z-VAD-FMK could attenuate the inhibitory effect of bortezomib on the proliferation of SNK-6 cells (P<0 .05), while bay11-7082 could enhance the inhibitory effect of bortezomib on the proliferation of snk-6 cells (P<0 .05). after treatment of snk-6 cells with bortezomib for 24 h, apoptosis-related protein caspase-3 cleavage, parp activation, and bcl-2 cleavage; nf-κb signaling pathway-related protein p65 phosphorylation level decreased, and p52 decreased.ConclusionBortezomib inhibits ENKTL cells proliferation by inhibiting NF-κB signaling pathway and induces apoptosis of ENKTL cells via mitochondria-mediated caspase pathway.
