呋喃二烯对人胃腺癌MGC-803细胞凋亡的诱导作用  

Induction of furanodiene on apoptosis of human gastric adenocarcinoma MGC-803 cells

作　　者：郭健敏 陈雨[2,3] 周云[2,3] 韩重 杨威 

机构地区：[1]广东省生物资源应用研究所药物非临床评价研究中心,广东广州510990 [2]广东莱恩医药研究院有限公司,广东广州510990 [3]广东药学院药科学院药理系,广东广州510006

出　　处：《中国药理学与毒理学杂志》2016年第3期215-220,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：国家科技重大专项(2013ZX0910-3001012)~~

摘　　要：目的研究呋喃二烯（FDE）在体外对人胃腺癌MGC-803细胞凋亡的诱导作用。方法 FDE46.29-740.74μmol·L^-1MGC-803细胞孵育48 h,MTT法测定FDE对细胞存活的抑制率;FDE 92.58-370.32μmol·L^-1MGC-803细胞作用24 h,光镜下及Hoechst 33342荧光染色分别观察细胞形态和细胞凋亡,流式细胞术检测细胞凋亡和细胞周期,罗丹明123染色和DCFH-DA荧光探针分别检测细胞线粒体膜电位的改变和活性氧的产生。结果 MTT结果表明,FDE 46.29-740.74μmol·L^-1MGC-803存活具有明显抑制作用,作用24,48和72 h时IC50分别为347.91,257.41和101.01μmol·L^-1流式细胞仪AnnexinⅤ-FITC/PI双染结果显示,FDE在92.58-370.32μmol·L^-1用24 h,能显著促进MGC-803细胞凋亡（P〈0.05）。细胞周期检测结果表明,FDE可使MGC-803细胞周期阻滞于S期。罗丹明123和DCFH-DA染色结果显示,当药物浓度为370.37μmol·L^-1,FDE使细胞内线粒体膜电位降低（P〈0.05）,对应荧光强度的细胞比例与对照组的比值为0.85∶1,使细胞内活性氧水平增加,活性氧水平为对照组的1.30倍（P〈0.05）。结论 FDE可抑制人胃腺癌MGC-803细胞存活,并诱导其凋亡,其诱导凋亡的作用机制可能与激活线粒体凋亡通路、影响细胞周期和抑制DNA的生物合成相关。OBJECTIVE To investigate the effect of furanodiene（FDE）,a diterpene derived from the medicinal plant Zedoary,on apoptosis of human gastric cancer MGC- 803 cells induced in vitro.METHODS MGC-803 cells were treated with FDE 46.29-740.74 μmol·L-1for 24,48 and 72 h,and the cell viability was detected with MTT assay. Cell morphology was observed by light microscopy and Hoechst33342 staining. Flow cytometry was used to detect cell apoptotic rate and cell cycle. Rh123 staining and fluorescence probe DCFH- DA were employed to detect the changes in mitochondrial membrane potential（MMP）and reactive oxygen species（ROS）. RESULTS MTT Results showed that FDE 46.29-740.74 μmol·L^-1exhibited significantly higher cytotoxicity to gastric cancer MGC-803 cells.IC50 for MGC-803 of 24,48 and 72 h treatment was 347.91,257.41 and 101.01 μmol·L^-1,respectively.Treatment with FDE 92.58-370.32 μmol·L^-1for 24 h also caused significant morphological changes in MGC-803 cells. AnnexinⅤ-FITC/PI double staining showed that the apoptotic rate increased after FDE 92.58-370.32 μmol·L^-1treatment for 24 h（P〈0.05）. FDE enabled MGC-803 cell cycle arrest in S phase. DCFHDA staining showed that FDE resulted in an increase in intracellular ROS levels（P〈0.05）when PDE concentration was 370.37 μmol·L^-1（P〈0.05）. MMP decreased after FDE treatment when PDE concentration was 370.37 μmol·L-1（P〈0.05）. CONCLUSION FDE Possesses potent tumor selected toxicity and can induce apoptosis of MGC-803 cells through cell cycle arresting,which is related to inhibition of DNA biosynthesis.

关 键 词：呋喃二烯 MGC-803细胞 胃癌 细胞凋亡 细胞周期 线粒体膜电位 活性氧 

分 类 号：R96[医药卫生—药理学]