中文摘要：

目的：探讨As2O3通过Notch信号通路对HepG2细胞凋亡的影响,阐明其作用机制。方法：体外培养的HepG2细胞分为空白组、As2O3组、MW167组和联合组;采用不同浓度As2O3和MW167处理HepG2细胞24、48和72h,MTT法检测细胞增殖抑制率。根据MTT结果选取无细胞毒剂量As2O3和MW167（As2O30.25mg·L^-1、MW167 10μmol·L^-1）分组干预HepG2细胞48h;流式细胞术检测细胞凋亡率;RT-PCR和Western blotting法检测Notch-1、Bcl-2和Caspase-3mRNA和蛋白表达水平。结果：不同浓度As2O3和MW167处理HepG2细胞均可抑制细胞增殖,呈剂量效应关系;无细胞毒剂量As2O3和MW167处理不同分组HepG2细胞48h后,与空白组比较,As2O3组、MW167组和联合组细胞凋亡率升高（P〈0.05）,其中以联合组升高最为明显;与空白组比较,As2O3组、MW167组和联合组细胞中Bcl-2、Notch-1mRNA和蛋白表达水平降低（P〈0.05）,其中以联合组降低最为明显;与空白组比较,As2O3组、MW167组和联合组细胞中Caspase-3mRNA和蛋白表达水平升高（P〈0.05）,其中以联合组升高最为明显。结论：As2O3可诱导肝癌HepG2细胞凋亡,其作用机制可能与通过Notch信号通路下调细胞中Bcl-2、Notch-1基因和蛋白表达水平以及上调细胞中Caspase-3基因和蛋白表达水平有关联。

英文摘要：

Objective To discuss the effect of As2O3 on the apoptosis of HepG2 cells via Notch signal pathway,and to clarify its mechanism.Methods The HepG2 cells cultured in vitro were divided into blank group,As2O3 group,MW167group and combination group.The HepG2 cells were treated with As2O3 and MW167at different concentrations for 24,48 and 72h,and the inhibitory rates of proliferations of the HepG2 cells were detected by MTT method.The HepG2 cells in various groups were intervened by MW167 and As2O3 at non-cytotoxic doses（As2O30.25mg·L^-1,MW167 10μmol·L^-1）based on the results of MTT for 48 h,then the apoptotic rate was tested by flow cytometry;RT-PCR and Western blotting methods were employed to detect the expressions of Notch-1,Bcl-2and Caspase-3mRNA and protein.Results The HepG2 cells treated with both As2O3 and MW167at different concentrations could inhibit the cell proliferation and showed a dose-effect relationship.For the HepG2 cells in different groups treated with MW167 group and As2O3 group at non-cytotoxic doses for 48 h,compared with blank group,the apoptotic rates in As2O3 group,MW167group and combination group were increased（P〈0.05）,especially in combination group;the expression levels of Bcl-2,Notch-1 mRNA and protein in As2O3 group,MW167group and combination group were lower than those in blank group（P〈0.05）,especially in combination group;compared with blank group,the expressions levels of Caspase-3mRNA and protein in As2O3 group,MW167group and combination group were increased（P〈0.05）,especially in combination group.Conclusion As2O3 can induce the apoptosis of hepatocelular carcinoma HepG2 cells and the mechanism may be related to the down-regulation of Bcl-2and Notch-1and up-regulation of Caspase-3 mRNA and protein through Notch signal pathway.