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三氧化二砷选择性诱导人肝癌细胞凋亡及 相关基因的实验研究
引用本文:刘琳,秦叔逵,陈惠英.三氧化二砷选择性诱导人肝癌细胞凋亡及 相关基因的实验研究[J].中华肝脏病杂志,2000,8(6):367-369.
作者姓名:刘琳  秦叔逵  陈惠英
作者单位:[1]解放军第八一医院全军肿瘤中心,南京210002 [2]南京中医药大学
基金项目:江苏省科委青年科技基金(BQ98048)
摘    要:目的 明确三氧化二砷对人肝癌细胞的诱导凋亡作用及其分子机制。方法 用四甲基偶氮唑蓝法、AO/EB荧光染色法、透射与扫描电镜观察、DNA电泳、流式细胞术、TUNEL法及免疫组织化学等方法,观察了三氧化二砷对体外培养的人肝癌细胞株QGY-7701、QGY-7703和正常人肝细胞株L-02的生长活力、细胞凋亡、细胞周期及其相关基因表达的影响。结果 三氧化二砷能显著地抑制人肝癌细胞QGY-7701和QGY-7703的生长,用药后诱导其出现了典型的细胞凋亡形态学和生化学改变,并使细胞周期阻滞于S期,且bcl-2基因表达明显下降,bax和Fas基因表达显著增强;三氧化二砷对正常人肝细胞株L-02无明显作用。结论 三氧化二砷对人肝癌细胞有显著的选择性诱导凋亡作用,且受到多种基因调控,这一结论为应用三氧化二砷治疗原发性肝癌提供了可靠的实验依据。

关 键 词:肝细胞癌  三氧化二砷  细胞凋亡
修稿时间:1999年9月22日

An experimental study on arsenic trioxide-selectively induced human hepatocarcinoma cell lines apoptosis and its related genes
LIU Lin,QIN Shukui,CHEN Huiying,et al..An experimental study on arsenic trioxide-selectively induced human hepatocarcinoma cell lines apoptosis and its related genes[J].Chinese Journal of Hepatology,2000,8(6):367-369.
Authors:LIU Lin  QIN Shukui  CHEN Huiying  
Institution:Tumor Center, the 81st hospital of PLA, Nanjing 210002, China.
Abstract:Objective: To study the possible apoptosis-inducing effect of arsenic trioxide on human hepatocarcinoma (HCC) cells, and its molecular mechanisms. Methods: Arsenic trioxide action on the cell growth, apoptosis, periodicity and the expression of related genes in two human hepatocarcinoma cell lines QGY-7701 and QGY-7703, and normal humanhepatic cell line L-02 in vitro was observed by MTT assay, acridine orange (AO) /ethidiumbromide (EB) fluorescent staining, electron microscopy detection, DNA gel electrophoresis, flow cytometry, TUNEL assay and immunohistochemical staining. Results: Arsenic trioxide could strongly inhibit the growth of human hepatocarcinoma cells QGY-7701 and QGY-7703 with the cell cycle arrested on S phase, and induce the apoptosis of the cells with bcl-2 gene expression down-regulated and bax and Fas gene expression up-regulated. But arsenic trioxide had no obvious effect on the normal hepatic cells. Conclusion: Arsenic trioxide has significant selective apoptosis-inducing effect on the human hepatocarcinoma cells, which is regulated by several genes. The results provide the credible experimental basis for clinically treating HCC with arsenic trioxide.
Keywords:Carcinoma  hepatocellular    Apoptosis    Gene    Arsenic trioxide
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