逆转录酶抑制剂对恶性胶质瘤细胞端粒酶活性和细胞增殖的影响

目的研究逆转录酶抑制剂（AZT）对胶质瘤细胞端粒酶活性、细胞增殖和细胞周期的影响，为以端粒酶为靶点治疗脑胶质瘤提供理论和实验依据。方法采用MTT法检测AZT对细胞生长增殖的影响。用TRAP—PCR—ELISA法检测端粒酶活性的变化。用流式细胞仪检测细胞周期的改变。结果与对照组比较，12h后1．0mol／L AZT组的端粒酶活性降低（P〈0.05），24h时0.5mol／L AZT组细胞生长增殖受抑制（P〈0．05），1．0mol／L AZT组则呈现出显著性差异（P〈0．01），在实验范围内，呈时间一剂量依赖性。实验组细胞周期中各时相的细胞分布发生改变，0．5mol／L AZT组细胞多阻滞于G2／M期，而1．0mol／L AZT组细胞G1期增多，S期细胞数减少。结论逆转录酶抑制剂能够有效地抑制胶质瘤细胞的端粒酶活性，抑制细胞的增殖，参与了细胞周期及凋亡的调控，具有较好的应用前景。

The effects of AZT on the telomerase activity and proliferation in malignant glioma cells

Objective To investigate the effects of AZT on telomerase activity and proliferation in malignant glioma cell line, so as to gain further insight about telomerase as the anti-cancer target of the therapy.Methods MTT method was used to detect the cell survival rate. Telomeric repeat amplification protocol (TRAP)-ELISA was used to examine the telomerase activity. Cell apoptosis rate and the phases of cell cycle were determined by flow cytometry (FCM).Results Compared with the control, addition of AZT inhibited telomerase activity and cell proliferation in time-dependent (12 h vs. 24 h) and dose-dependent (0.5 mol/L vs. 1.0 mol/L) manners (P<0.05-0.01).AZT changed the normal pattern of cell cycle:in 0.5 mol/L group, most cells were arrested at G_2/M phase; while in 1.0 mol/L grouop,G_1 phase cells were increased and S phase cells were decreased.Conclusion AZT inhibits glioma cell proliferation and telomerase activity, takes part in regulating cell cycle and cell apoptosis,and therefore,will have the potential to play a role in glioma treatment.