木脂素-1通过抑制DNA拓扑异构酶Ⅰ诱导胃癌细胞凋亡的机制研究  

Study on the mechanism of lignan-1 inducing apoptosis of gastric cancer cells by inhibiting DNA topoisomerase Ⅰ

作　　者：娄红刚 张琛涵 康富贵 聂静云 柴琛[2] LOU Honggang;ZHANG Chenhan;KANG Fugui;NIE Jingyun;CHAI Chen(The First Clinical Medical College of Lanzhou University,Lanzhou,Gansu,China,730000;The First Clinical Medical College of Lanzhou University,People's Hospital of Suzhou High-tech Zone,Suzhou,Jiang-su,China,215129)

机构地区：[1]兰州大学第一临床医学院,甘肃兰州730000 [2]兰州大学第一临床医学院,苏州高新区人民医院,江苏苏州215129

出　　处：《分子诊断与治疗杂志》2021年第8期1251-1254,1259,共5页Journal of Molecular Diagnostics and Therapy

基　　金：甘肃省中医药管理局科研项目(GZK⁃2011⁃62)。

摘　　要：目的探究牛蒡子衍生物木脂素-1(Mzs-1)体外抗肿瘤活性,初步分析其诱导胃癌细胞凋亡相关机制,为临床提供参考依据。方法采用CCK-8法测定Mzs-1对人胃癌细胞株SGC-7901增殖抑制情况,计算其半数抑制浓度(IC50),并观察Mzs-1对SGC-7901细胞凋亡及细胞周期的影响,分析Mzs-1对DNA拓扑异构酶Ⅰ(TopoⅠ)活性、SGC-7901细胞TopoⅠ蛋白表达的影响。结果 Mzs-1能抑制人胃癌细胞株SGC-7901增殖活性,且存在时间-浓度依赖性(P<0.05);不同浓度Mzs-1处理SGC-7901细胞48 h后,各组早期凋亡细胞比率差异有统计学意义(P<0.05);不同浓度Mzs-1作用于SGC-7901细胞48 h后,各组处于G2/M期细胞比例差异有统计学意义(P<0.05);Mzs-1处理SGC-7901细胞48 h后,各组TopoⅠ蛋白相对表达量差异有统计学意义(P<0.05);Mzs-1能抑制SGC-7901细胞中TopoⅠ活性、下调TopoⅠ蛋白表达,且存在浓度依赖性。结论 Mzs-1具有抗人胃癌细胞株SGC-7901增殖作用,并通过阻滞SGC-7901细胞周期于G2/M期而诱导其细胞株凋亡,作用机制可能与Mzs-1抑制SGC-7901细胞内TopoⅠ活性、下调TopoⅠ蛋白表达有关。Objective To explore the anti-tumor activity of burdock seed derivative lignan-1(Mzs-1)in vitro,and analyze its mechanism of inducing apoptosis of gastric cancer cells to provide clinical reference. Methods The inhibition of Mzs-1 on the proliferation of human gastric cancer cell line SGC-7901 was determined by CCK-8 method. The 50% concentration of inhibition(IC50)of MZS-1 was calculated,and the effect of MZS-1 on apoptosis and cell cycle of SGC-7901 cells was observed. The effect of Mzs-1 on DNA topoisomerase Ⅰ(Topo Ⅰ)activity and Topo Ⅰ protein expression in SGC-7901 cells was analyzed. Results MZS-1 can inhibit the proliferation of human gastric cancer cell line SGC-7901 in a time-concentration dependent manner. The IC50 value of MZS-1 against SGC-7901 was 38.56μg/mL. After treatment with MZS-1 for48 h,the ratio of apoptotic cells and G2/M phase cells increased with the increase of drug concentration.MZS-1 inhibits the activity of TOPO Ⅰ and down-regulates the expression of TOPO Ⅰ protein in SGC-7901 cells in a concentration-dependent manner. Conclusion Mzs-1 has the anti-proliferation effect of human gastric cancer cell line SGC-7901,and induces cell apoptosis by blocking SGC-7901 cell cycle in G2/M phase. The mechanism of action may be related to Mzs-1.s inhibition of Topo Ⅰ activity in SGC-7901 cells and down-regulation of Topo Ⅰ protein expression.

关 键 词：木脂素-1 人胃癌细胞株SGC-7901 DNA拓扑异构酶Ⅰ 

分 类 号：R735.2[医药卫生—肿瘤]