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两种聚腺苷二磷酸核糖聚合酶1抑制剂对人肝癌细胞株HepG2增殖和凋亡的影响
Effects of PARP-1 inhibitors AG-014699 and AZD2281 on proliferation and apoptosis of human hepatoma cell line HepG2
文章发布日期:2015年05月08日  来源:  作者:杜森荣,毛小荣,肖萍,等  点击次数:1396次  下载次数:351次

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【摘要】:目的观察聚腺苷二磷酸核糖聚合酶(PARP)-1抑制剂AG-014699和AZD2281对人肝癌细胞株HepG2细胞抑制作用和凋亡,初步探讨PARP-1抑制剂诱导HepG2细胞凋亡的机制,为肝癌提供一种新的治疗靶点。方法 MTT实验观察不同浓度的AG-014699和AZD2281对HepG2细胞增殖的影响,用流式细胞术检测HepG2细胞凋亡率;Western Blot法检测casepase3和casepase8蛋白表达水平。组间比较采用t检验。结果AG014699和AZD2281均有抑制HepG2细胞增殖的作用,且具有时间和浓度依赖性,但HepG2细胞对两种PARP-1抑制剂的敏感性不同,用MTT法检测48 h AG-014699和AZD2281的IC50分别约为20、400 μmol/L。因AZD2281不敏感,未做流式细胞术和Western Blot法检测细胞凋亡。用10、30、50 μmol/L的AG-014699能诱导HepG2细胞凋亡,48 h时凋亡率最高达(3100±213)%,明显高于对照组(0.900±0013)%,二者差异有统计学意义(P<0.01)。30、50μmol/L的AG-014699作用HepG2细胞48 h后的caspase3和caspase8蛋白水平相对于正常对照组显著增加。结论PARP-1抑制剂AG-014699和AZD2281均能抑制HepG2细胞增殖,但敏感性不同,AG-014699可诱导HepG2细胞凋亡,通过上调caspase3和caspase8蛋白水平来诱导细胞凋亡。
【Abstract】:ObjectiveTo observe the inhibitory and pro-apoptotic effects of two poly(ADP-ribose) polymerase (PARP-1) inhibitors, AG-014699 and AZD2281, on human hepatoma HepG2 cells and preliminarily explore the mechanism by which AG-014699 induces HepG2 cell apoptosis, and to provide a new therapeutic target for hepatoma. MethodsThe effects of different concentrations of AG-014699 and AZD2281 on HepG2 cell proliferation were determined by MTT assay. The cell apoptosis rate was measured by flow cytometry. The expression levels of caspase-3 and caspase-8 were measured by Western Blot. Inter-group comparison was made by t test. ResultsBoth AG-014699 and AZD2281 suppressed HepG2 cell proliferation in a time- and dose-dependent manner. However, the sensitivity of HepG2 cells to the two PARP-1 inhibitors was different. The half-maximal inhibitory concentrations of AG-014699 and AZD2281 at 48 h determined by MTT assay were about 20 μmol/L and 400 μmol/L, respectively. Flow cytometry and Western blot were not used to evaluate the apoptosis of HepG2 cells exposed to AZD2281 to which these cells were not sensitive. HepG2 cell apoptosis could be induced by 10, 30, and 50 μmol/L AG-014699, and the highest apoptosis rate at 48 h was significantly higher than that of the control group (3100%±2.13% vs 09%±0013%, P<0.01). Compared with those in the control group, the protein levels of caspase-3 and caspase-8 in HepG2 cells after 48-h exposure to 30, and 50 μmol/L AG-014699 increased. ConclusionThe two PARP-1 inhibitors AG-014699 and AZD2281 can inhibit the proliferation of HepG2 cells, which showed different sensitivities to the two inhibitors. AG-014699 can induce HepG2 cell apoptosis by up-regulating the protein expression of caspase-3 and caspase-8.
【关键字】:肝肿瘤;聚ADP核糖聚合酶类;酶抑制剂;HepG2细胞;细胞增殖;细胞凋亡
【Key words】:liver neoplasms; poly(ADP-ribose) polymerases; enzyme inhibitors; HepG2 cell line; cell proliferation; apoptosis
【引证本文】:

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