蛋白酶体抑制剂MG132对NK/T淋巴瘤细胞增殖、凋亡和细胞周期的影响

Effect of proteasome inhibitor MG132 on proliferation and cell cycle distribution of NK/T cell lymphoma cells

目的:探讨蛋白酶体抑制剂MG132(Z-leu-leu-leu-CHO,三肽基乙醛)对NK/T淋巴瘤细胞的增殖和细胞周期分布的影响,研究蛋白酶体抑制剂MG132治疗NK/T细胞淋巴瘤的潜在应用价值。方法:用蛋白酶体抑制剂MG132处理细胞,噻唑蓝[3(4,5二甲基噻唑2)2,5二苯基四氮唑溴盐,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT]法检测细胞增殖抑制率,倒置显微镜观察细胞形态改变,流式细胞仪检测细胞周期分布和凋亡。结果:1μmol/LMG132作用24h,HANK1细胞增殖抑制率为(57.72±7.44)%,而0.1μmol/LMG132作用24h,增殖抑制率仅为(3.98±0.07)%;MG132剂量大,增殖抑制率高;1μmol/LMG132作用24h后,HANK1细胞G1和G2期细胞分别为(72.33±3.44)%和(12.86±1.29)%,对照组为(63.63±2.29)%和(7.94±1.91)%,用药组G1和G2期细胞明显高于对照组(P<0.01,P<0.05);早期凋亡细胞和晚期凋亡细胞分别为(33.57±2.10)%和(16.66±0.47)%,而对照组仅为(7.18±0.82)%和(3.81±1.06)%,与对照组相比,凋亡率明显增高(P<0.01,P<0.01)。结论:MG132抑制NK/T细胞淋巴瘤细胞增殖,使细胞周期G1和G2期阻滞,促进细胞凋亡,并存在剂量和时间依赖关系,蛋白酶体抑制剂MG132很可能成为治疗进展期NK/T细胞淋巴瘤的药物。

AIM： To study the influence of MG132 on the proliferation and cell cycle distribution of NK/T cell lymphoma cells, and to investigate the potential role of proteasome inhibitor on the treatment of NK/T cell lymphoma. METHODS： NK/T cell lymphoma cells HANK1 were treated with proteasome inhibitor MG132, and the proliferation was evaluated by MTT assay. The morphological changes were observed under inverse microscope. The cell cycle distribution and apoptosis were detected using flow cytometry. RESULTS： The growth inhibitory rate of HANKI cells was （57. 72 ± 7.44）% after cultured for 24 h with 1 μmol/L MG132 and was just（3.98±0.07）% after cultured for 24 h with 0. 1 μmol/L MG132. The positive relationship between the concentration of MG132 and growth inhibitory rate was observed. On the other hand, after cultured for 24 h with 1μmol/L MG132, the cells in G1 and G2 phases were （72. 33± 3.44 ） % and （ 12. 86 ±1.29） %, respectively, much higher than those in control group（63.63%± 2. 29% and 7. 94% ± 1.91%, respectively）. The early and late apoptosis rates in MG132 group were 33.57% ± 2. 10% and 16. 66% ± 0.47%, respectively, much higher than that in control group （7. 18% -0. 82% and 3.81%± 1.06% , respectively）. CONCLUSION： MG132 inhibits cell proliferation and induces cell cycle arrested at G1 and G2 phases, and cell apoptosis in NK/T cell lymphoma cells in a concentration dependent manner. Proteasome inhibitor may be a good drug to treat patients with advanced NK/T cell lymphomas.