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曲古菌素A对人胰腺癌PaTu-8988细胞增殖和细胞周期的影响

Effects of inhibitors of trichostatin A on the growth and cell cycle of PaTu-8988 cell lines
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摘要 目的 观察曲古菌素A(trichostatin A,TSA)对人胰腺癌PaTu-8988细胞增殖及细胞周期的影响。方法不同浓度(0.1、0.5、2.0μmol/L)TSA处理人胰腺癌PaTu-8988细胞,并设空白对照组。采用WST-8法检测细胞存活率;流式细胞仪检测细胞周期的变化;实时定量PCR检测细胞周期相关基因p21和cyclinD1mRNA的表达。结果对照组、TSA0.1μmol/L、0.5μmol/L和2.0μmol/L组的细胞存活率分别为(100.0±4.2)%、(88.5±4.2)%、(79.7±5、0)%和(64、3±7.2)%,各TSA组均显著低于对照组(P〈0.01)。TSA0.1μmol/L、0.5μmol/L组的细胞以G1期居多,2.0μmol/L组(50.29±7.53)%细胞阻滞在G2/M期。TSA各组p21mRNA表达值分别为5、29±1.16、7.79±0.41、8.61±0.73,较对照组1.00±0.08显著升高(P〈0.01);cyclin D1mRNA表达值分别为1.134-0、12、0.42±0.06、0.19±0.06,较对照组1.00±0.07表达降低(P〈0.05)。结论TSA通过上调p21及下调cyclinD1基因的表达,导致细胞周期阻滞。 Objective To investigate the effect of trichostatin A (TSA) on inhibition of cell proliferation and cell cycle of human pancreatic cancer cell line PaTu-8988 in vitro. Methods PaTu-8988 cells were treated with different concentration TSA (0. 1, 0. 5, 2.0 μmol/L), and blank control group was used. The growth inhibition rates of cells were measured by WST-8 method. Cell cycle and apoptosis were detected by flow cytometry; the expressions of p21 mRNA and HDAC1 mRNA were measured by Real-Time PCR. Results Survival rates of TSA 0. 1 μmol/L, 0. 5 μmol/L and 2.0 μmol/L group was ( 88.5 ±4.2 ) %, ( 79.7± 5.0 ) % and ( 64.3 ± 7.2 ) %, respectively, which were all significantly lower than ( 100.0 ± 4.2 ) % of the blank control group ( P 〈0. 01 ). Cells in the group of TSA 0. 1 μmol/L and 0. 5 μmol/L were hindered at G2 phase, while (50.29 + 7.53)% of the cells in the group of TSA 2.0 μmol/L were hindered at G2/M phase. The expression rates of p21 mRNA in different TSA group were 5.29 ± 1.16, 7.79 ± 0. 41, 8.61± 0. 73, respectively, which were higher than that in the control group ( 1.00 ±0.08, P 〈0. 01 ) ; the expression rates of Cyclin D1 mRNA were 1.13 ± 0. 12, 0. 42 ±0. 06, 0. 19 ± 0. 06, respectively, which were higher than that in the control group ( 1.00 ± 0. 07, P 〈 0. 05 ). Conclusions TSA may up-regulate the expression of p21 and down-regulate the expression of cyclin D1, and induce cell cycle blockade.
出处 《中华胰腺病杂志》 CAS 2008年第4期234-236,共3页 Chinese Journal of Pancreatology
关键词 胰腺肿瘤 曲古菌素A 组蛋白脱乙酰基酶类 细胞周期 Pancreatic neoplasms Trichostatin A Histone deacetylases Cell cycle
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