论文部分内容阅读
目的:探讨糖原合酶激酶-3β(GSK-3β)抑制剂TDZD-8(4-苄基-2-甲基-1,2,4-噻二唑烷-3,5-二酮)对大鼠C6胶质细胞瘤细胞增殖的抑制作用及诱导凋亡的机制。方法:采用MTT方法检测TDZD-8不同浓度(10、20、40和80μmol/L)处理大鼠C6胶质细胞瘤细胞6、12、24和48 h后对细胞增殖的影响;流式细胞术检测其对细胞凋亡和细胞周期的作用,同时分析凋亡相关基因Bax、Bcl-2和P53的表达变化。结果:TDZD-8浓度、时间依赖性的抑制大鼠C6胶质细胞瘤细胞的增殖(P<0.05)。流式细胞术显示TDZD-8浓度依赖诱导细胞凋亡,其中在20、40和80μmol/L组有统计学差异(P<0.05)。40和80μmol/L TDZD-8处理C6细胞后,G0/G1期细胞数量明显增多,分别升高到83%和90%(P<0.05);而S期和G2/M期细胞数则显著降低(P<0.05)。同时,40和80μmol/L TDZD-8使Bax和P53表达显著增加,而使Bcl-2表达降低(P均<0.05)。结论:GSK-3β抑制剂TDZD-8可以浓度依赖性抑制C6细胞增殖同时诱导其凋亡,并引起细胞周期阻滞,这可能与其对Bax、P53和Bcl-2的调控相关。
Objective: To investigate the effect of TDZD-8 (4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione) on glycogen synthase kinase-3β Inhibition of rat C6 glioma cell proliferation and its mechanism of apoptosis. Methods: The effects of TDZD-8 on the proliferation of C6 glioma cells treated with different concentrations of 10, 20, 40 and 80 μmol / L for 6, 12, 24 and 48 h were detected by MTT assay. Flow cytometry The apoptosis and cell cycle were detected. The expression of Bax, Bcl-2 and P53 were also analyzed. Results: TDZD-8 inhibited the proliferation of rat C6 glioma cells in a concentration-dependent and time-dependent manner (P <0.05). Flow cytometry showed that TDZD-8 concentration-dependently induced apoptosis, with statistical significance at 20, 40 and 80 μmol / L groups (P <0.05). After treated with 40 and 80μmol / L TDZD-8, the number of cells in G0 / G1 phase increased significantly to 83% and 90% (P <0.05), while the cell number in S phase and G2 / M phase decreased significantly (P <0.05). At the same time, the expression of Bax and P53 was significantly increased by 40 and 80μmol / L TDZD-8, while the expression of Bcl-2 was decreased (all P <0.05). Conclusion: GSK-3β inhibitor TDZD-8 can inhibit the proliferation of C6 cells in a concentration-dependent manner and induce cell cycle arrest in a concentration-dependent manner, which may be related to the regulation of Bax, P53 and Bcl-2.