骆驼蓬碱对胃癌细胞增殖、凋亡的影响及其机制研究  

Effect and Underlying Mechanism of Harmine on Proliferation and Apoptosis of Gastric Cancer Cells

作　　者：张婷[1] 蒋世烨 金星星 张文灵 余纳 李晓林[1] 朱国琴[1] 周逸婵[1] 邵耘[1] 孙为豪[1] ZHANG Ting;JIANG Shiye;JIN Xingxing;ZHANG Wenling;YU Na;LI Xiaolin;ZHU Guoqin;ZHOU Yichan;SHAO Yun;SUN Weihao(Department of Geriatric Gastroenterology,the First Affiliated Hospital of Nanjing Medical University,Nanjing(210029))

机构地区：[1]南京医科大学第一附属医院老年消化科,210029

出　　处：《胃肠病学》2018年第4期221-225,共5页Chinese Journal of Gastroenterology

摘　　要：背景:骆驼蓬碱可通过下调环氧合酶-2(COX-2)表达抑制胃癌细胞增殖,但其分子机制尚未完全明确。目的:研究骆驼蓬碱对胃癌细胞增殖、凋亡的影响,探讨PTEN/Akt/MDM2信号通路在该过程中的作用。方法:以不同浓度(2、4、8、16、32μg/m L)骆驼蓬碱干预人胃腺癌细胞株SGC-7901和MKN-45 24 h、48 h和72 h,分别采用MTT法和Hoechst染色检测细胞增殖和凋亡情况;蛋白质印迹法检测PTEN、COX-2表达以及Akt、MDM2磷酸化水平。结果:骆驼蓬碱呈剂量和时间依赖性地抑制SGC-7901、MKN-45细胞增殖,并诱导其发生典型的凋亡形态学改变。骆驼蓬碱呈剂量依赖性地上调PTEN表达、抑制Akt、MDM2磷酸化以及COX-2表达。结论:骆驼蓬碱可能通过PTEN/Akt/MDM2信号通路下调COX-2表达,抑制胃癌细胞增殖并诱导其凋亡。Background:Previous study has found that harmine inhibited the proliferation of gastric cancer cells by down-regulating cyclooxygenase-2(COX-2)expression.However,its molecular mechanism is not fully clear.Aims:To investigate the effect of harmine on proliferation and apoptosis of gastric cancer cells,and explore the role of PTEN/Akt/MDM2 signaling pathway in this process.Methods:Human gastric adenocarcinoma cell line SGC-7901 and MKN-45 were treated with harmine at different concentrations(2,4,8,16,32μg/mL)for 24,48,and 72 hours.The cell proliferation and apoptosis were detected by MTT assay and Hoechst staining,respectively.The expressions of PTEN,COX-2,phosphorylated Akt(p-Akt)and p-MDM2 were measured by Western blotting.Results:Harmine dose-and time-dependently inhibited proliferation and induced apoptosis of SGC-7901 and MKN-45 cells.Also,harmine dose-dependently increased PTEN expression,and inhibited p-Akt,p-MDM2 and COX-2 expressions in SGC-7901 and MKN-45 cells.Conclusions:Harmine may inhibit proliferation and induce apoptosis of gastric cancer cells via down-regulating COX-2 expression through PTEN/Akt/MDM2 signaling pathway.

关 键 词：骆驼蓬碱 胃肿瘤 环氧合酶2 信号传导 细胞增殖 细胞凋亡 

分 类 号：R285[医药卫生—中药学]