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目的通过体外细胞培养观察硼替佐米和来那度胺对NK/T细胞淋巴瘤(NK/TCL)细胞株凋亡的作用,寻找治疗NK/T淋巴瘤的潜在药物。方法利用台盼蓝拒染法检测细胞活力及计数细胞,流式细胞术检测细胞凋亡和细胞周期分布,Annexin V/PI法检测细胞凋亡。结果硼替佐米对SNK-1、SNK-6、SNT-8有明显的细胞毒作用,在临床治疗浓度下显著诱导凋亡而减少细胞的存活。硼替佐米(30 nmol/L)作用24 h,SNK-1、SNK-6、SNT-8细胞存活比例分别为(47.2±3.5)%、(33.5±3.9)%、(52.1±4.3)%,与对照组相比差异均有统计学意义(P<0.01)。硼替佐米对3种细胞株活性抑制IC50的浓度分别为19.5、12.7、20.7 nmol/L。流式细胞术对细胞凋亡检测发现硼替佐米对SNK-1(30 nmol/L)、SNK-6(10 nmol/L)、SNT-8(30 nmol/L)细胞株均有显著的诱导凋亡作用,作用24 h后凋亡率为(47.0±4.2)%、(43.0±3.8)%、(53.0±4.1)%。来那度胺对3种细胞株的存活和增殖无显著作用,对细胞周期的分布也无明显影响。来那度胺联合硼替佐米无协同促进细胞凋亡作用。结论硼替佐米是选择性的蛋白酶体抑制剂,具有诱导NK/TCL细胞株凋亡的作用,可能有成为NK/TCL治疗药物的潜在价值。来那度胺在体外实验中对NK/TCL细胞株无显著作用,与硼替佐米亦无协同作用,体内是否具有抗肿瘤活性尚需进一步的研究。
Objective To observe the effect of bortezomib and lenalidomide on the apoptosis of NK / T cell lymphoma (NK / TCL) cell lines in vitro and to find out the potential drug for the treatment of NK / T lymphoma. Methods Cell viability was measured by trypan blue exclusion method. Cell apoptosis and cell cycle distribution were measured by flow cytometry. Apoptosis was detected by Annexin V / PI assay. Results Bortezomib had obvious cytotoxic effect on SNK-1, SNK-6 and SNT-8, and significantly induced apoptosis and decreased cell survival at clinical treatment concentrations. The survival rates of SNK-1, SNK-6 and SNT-8 were (47.2 ± 3.5)%, (33.5 ± 3.9)% and (52.1 ± 4.3)%, respectively after treated with bortezomib (30 nmol / L) Compared with the control group, the differences were statistically significant (P <0.01). The IC50 concentrations of bortezomib on the three cell lines were 19.5, 12.7 and 20.7 nmol / L, respectively. Flow cytometry showed that bortezomib significantly induced SNK-1 (30 nmol / L), SNK-6 (10 nmol / L) and SNT-8 The apoptotic rate was (47.0 ± 4.2)%, (43.0 ± 3.8)% and (53.0 ± 4.1)%, respectively. Lenalidomide had no significant effect on the survival and proliferation of the three cell lines and had no significant effect on the cell cycle distribution. Lenalidomide combined with bortezomib has no synergistic effect on apoptosis. CONCLUSION Bortezomib is a selective inhibitor of proteasome and induces the apoptosis of NK / TCL cell lines, which may be potential value of NK / TCL treatment. Lenalidomide had no significant effect on NK / TCL cell lines in vitro and no synergistic effect with bortezomib. Whether in vivo antitumor activity still needs further study.