首页> 外文期刊>World Journal of Gastroenterology >Synergistic effect of cell differential agent-II and arsenic trioxide on induction of cell cycle arrest and apoptosis in hepatoma cells
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Synergistic effect of cell differential agent-II and arsenic trioxide on induction of cell cycle arrest and apoptosis in hepatoma cells

机译:细胞分化剂-II和三氧化二砷对肝癌细胞诱导的细胞周期停滞和凋亡的协同作用

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AIM: To illustrate the possible role of cell differential agent-II (CDA-II) in the apoptosis of hepatoma cells induced by arsenic trioxide (As_2O_3). METHODS: Hepatoma cell lines BEL-7402 and HepG2 were treated with As_2O_3 together with CDA-II. Cell surviving fraction was determined by MTT assay; morphological changes were observed by immunofluorescence staining of Hoechst 33 258; and cell cycle and the apoptosis index were determined by flow cytometry (FCM). RESULTS: Cytotoxity of CDA-II was low. Nevertheless, CDA-II could strongly potentiate arsenic trioxide-induced apoptosis. At 1.0 g/L CDA-II, IC_(50) of As_2O_3 in hepatoma cell lines was reduced from 5.0 μmol/L to 1.0 μmol/L (P<0.01). The potentiation of apoptosis was dependent on the dosage of CDA-II. FCM indicated that in hepatoma, cell growth was inhibited by CDA-II at lower concentrations (<2.0 g/L) primarily by arresting at S and G_2 phase, and at higher concentrations (>2.0 g/L) apoptotic cell and cell cycle arresting at G_1 phase increased proportionally. The combination of two drugs led to much higher apoptotic rates, as compared with the either drug used alone. CONCLUSION: CDA-II can strongly potentiate As_2O_3-induced apoptosis in hepatoma cells, and two drugs can produce a significant synergic effect.
机译:目的:阐明细胞分化剂-II(CDA-II)在三氧化二砷(As_2O_3)诱导的肝癌细胞凋亡中的可能作用。方法:用As_2O_3和CDA-II处理肝癌细胞BEL-7402和HepG2。通过MTT测定法测定细胞存活分数;通过Hoechst 33 258的免疫荧光染色观察到形态学变化。流式细胞仪(FCM)测定细胞周期和凋亡指数。结果:CDA-II的细胞毒性较低。然而,CDA-II可以强烈增强三氧化二砷诱导的细胞凋亡。在1.0 g / L CDA-II下,肝癌细胞系中As_2O_3的IC_(50)从5.0μmol/ L降低至1.0μmol/ L(P <0.01)。凋亡的增强取决于CDA-II的剂量。 FCM表明,在肝癌中,CDA-II在较低浓度(<2.0 g / L)时抑制细胞生长,主要是通过阻滞在S和G_2期,而在较高浓度(> 2.0 g / L)时则凋亡细胞和细胞周期阻滞在G_1阶段按比例增加。与单独使用的任何一种药物相比,两种药物的组合导致更高的凋亡率。结论:CDA-II可强烈增强As_2O_3诱导的肝癌细胞凋亡,两种药物可产生明显的协同作用。

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