Abstract: Objective To investigate the influence of polyamine analogue DENSPM (N1, N11- diethylnorspermine) on cell growth of human SNB19 glioblastoma cells. Methods DENSPM was added into the culture medium of SNB19 cells. MTS assay was used to assess cell survival rate. The change of the cell cycle and the value of intracellular H2O2 were evaluated by flow cytometry. The level of polyamine was measured by HPLC. The expression of ornithine decarboxylase (ODC), spermidine/spermine N(1)-acetyltransferase (SSAT), polyamine oxidase (PAO) mRNA was identified by quantitative RT-PCR. Results Cell survival rate of SNB19 cells decreased markedly after DENSPM treatment (F = 81.915, P = 0.001). DENSPM treatment led to the appearance of typical sub-G1 peak in flow cytometry assay. The levels of putrescine, spermidine and spermine reduced (P < 0.01), while the level of acetylspermidine and acetylspermine slightly increased (P < 0.01). Meanwhile, the mRNA expression of ODC decreased (P < 0.01). The level of SSAT and PAO increased (P < 0.01, P < 0.05, respectively). However, the value of intracellular H2O2 was unchanged (P > 0.05). Conclusion The polyamine analogue DENSPM inhibits cell growth and induces apoptosis of SNB19 glioblastoma cells. Reduction of polyamine in SNB19 cells is the possible mechanism of apoptosis. DENSPM may be a potential medication for glioblastoma.

Key words: Glioblastoma, Polyamine analogue, Tumor cells, cultured, Apoptosis

摘要： 目的 探讨多胺类似物DENSPM 对人胶质母细胞瘤SNB19细胞生长的影响。方法 采用MTS 法、流式细胞术、高效液相色谱法和逆转录-聚合酶链反应，分别检测经DENSPM 处理后的SNB19 细胞存活率、细胞周期变化和细胞内过氧化氢水平，以及细胞内多胺水平和鸟氨酸脱羧酶、亚精胺/精胺-N1-乙酰基转移酶、多胺氧化酶mRNA 表达变化。结果 经DENSPM 处理后，SNB19 细胞存活率随着药物浓度的增加逐渐降低（F = 81.915，P = 0.001），并于体外培养72 h 在细胞增殖周期中出现典型的亚凋亡峰；细胞内腐胺、亚精胺和精胺水平显著下降，而乙酰亚精胺和乙酰精胺水平略有上升（均P < 0.01）；鸟氨酸脱羧酶表达水平下降（P < 0.01），而亚精胺/精胺-N1-乙酰基转移酶和多胺氧化酶水平上升（P < 0.05或P < 0.01）；但细胞内过氧化氢水平与DENSPM 处理前差异无统计学意义（P > 0.05）。结论 DENSPM可抑制人胶质母细胞瘤SNB19 细胞的生长并诱导其发生凋亡，而诱导细胞凋亡的可能机制是肿瘤细胞内多胺表达水平下降。DENSPM 可能具有治疗胶质母细胞瘤的潜在临床应用价值

关键词: 胶质母细胞瘤, 多胺类似物, 肿瘤细胞, 培养的, 细胞凋亡