中文摘要：

目的研究苯甲醛左氧氟沙星席夫碱化合物对人肝癌SMMC-7721细胞凋亡的诱导作用。方法用不同浓度的（S）-1,8-（2-甲基亚乙氧基）-6-氟-7-（4-甲基-哌嗪-1-基）-3-[S-苄基硫基-4-（对硝基苯甲叉基氨基）-1,2,4-均三唑-3-基]-喹啉（1-H）-4-酮（M18）与SMMC-7721细胞、人乳腺癌细胞MB-231、人结肠癌细胞HCT-116、人肝癌细胞HEPG-2和小鼠骨髓间充质干细胞体外培养。MTT法检测M18对各种细胞的生长抑制作用;Hoechst 33258荧光染色法、TUNEL法检测细胞凋亡变化;高内涵活细胞成像系统测定细胞线粒体膜电位（△ψm）变化;Western blot方法测定caspase-3、p53蛋白表达量的改变,以及细胞色素C在线粒体内外的分布。结果 M18在4-32μmol·L^-1的浓度范围内能明显抑制SMMC-7721细胞、MB-231细胞、HCT-116细胞、HEPG-2细胞增殖,呈浓度、时间依赖关系,作用于细胞24 h的IC50值分别为8.65、9.37、12.74和9.40μmol·L^-1;左氧氟沙星盐酸盐作用于SMMC-7721细胞24 h的IC50值为735.10μmol·L^-1,M18作用于骨髓间充质干细胞24 h的IC50值为38.96μmol·L^-1;不同浓度M18作用人肝癌SMMC-7721细胞24h,细胞凋亡率高于对照组（P〈0.05）。M18作用于SMMC-7721细胞后,细胞线粒体膜电位降低,与对照组相比差异有统计学意义;M18明显增加SMMC-7721细胞的p53和caspase-3蛋白表达量,其中caspase-3活性裂解片段增加明显;M18作用使细胞线粒体内细胞色素C明显减少,胞质内细胞色素C明显增加。结论苯甲醛左氧氟沙星席夫碱能够诱导人肝癌细胞凋亡,作用与线粒体凋亡通路有关。

英文摘要：

Aim To study the effect of （S） -1, 8-（2-methyl phosphate ethoxy ）-6-fluorine-7-（ 4-methyl- pi-perazine-1-base ）-3-[ S-benzyls-based-4-（ for nitroben-zene methylene group amino ）-1 , 2 , 4-all triazole-3 base]-quinoline （ 1-H ）-4-ketone （ M18 ） on apoptosis of hepatocarcinoma SMMC-7721 cells in vitro. Meth-ods With different concentrations of M18 at different time used to treat SMMC-7721 cells, human breast cancer MB-231cells, human colon cancer HCT-116 cells, human hepatocarcinoma HEPG-2 cells, mouse bone marrow mesenchymal stem cells （ BMSCs ） in vitro,the inhibition effects of M18 on cell proliferation were examined by MTT assay. Cell apoptosis was de-termined using Hoechst 33258 fluorescence staining and TUNEL method. Mitochondrial membrane poten-tial （△ψm ） was measured using a high content screening image system. Protein expression of caspase-3 , p53 and cytochrome C was detected with Western blot analysis. Results Treatment with M18 （ 4 -32μmol·L^-1 ） potently inhibited the proliferation of the cancer cells in time-and dose-dependent manners （ the IC50 value at 24 h in SMMC-7721 cells, MB-231cells, HCT-116 cells and HEPG-2 cells was 8. 65 μmol · L^-1 , 9. 37 μmol · L^-1 , 12. 74 μmol · L-1 and 9. 40μmol · L^-1 , respectively ） . In contrast, M18 had weak cytotoxicity against BMSCs with IC50 value of 38. 96 μmol·L^-1 . Levofloxacin had weak cytotoxicity against SMMC-7721 cells with IC50 value of 735. 10μmol·L^-1 . Treatment of SMMC-7721cells with differ-ent concentrations of M18 for 24 h increased the per-centage of the apoptosis cells （ P 〈0. 05 ） and de-creased the mitochondrial membrane potential. In ad-dition, M18 increased protein expression of p53, caspase-3 and the cleaved activated forms of caspase-3 in SMMC-7721 cells. Treatment of SMMC-7721 cells with M18 significantly increased cytochrome C in the cytosol, and decreased cytochrome C in the mitochon-drial compartment. Conclusion The mitochondrial-dependent pathways are involved in M18