[1]霍 菲,唐乃夫,范媛媛,等.苯甲醛左氧氟沙星席夫碱诱导人肝癌细胞凋亡作用[J].中国药理学通报,2015,(06):821-826.
 HUO Fei,TANG Nai-fu,FAN Yuan-yuan,et al.Benzaldehyde levofloxacin schiff base induces apoptosis of human hepatocarcinoma cells[J].Chinese Pharmacological Bulletin,2015,(06):821-826.
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苯甲醛左氧氟沙星席夫碱诱导人肝癌细胞凋亡作用()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2015年06期
页码:
821-826
栏目:
论 著
出版日期:
2015-06-15

文章信息/Info

Title:
Benzaldehyde levofloxacin schiff base induces apoptosis of human hepatocarcinoma cells
作者:
霍 菲1唐乃夫1范媛媛1刘诗濛2张 莹2梁红霞1胡国强3刘 彬1
河南大学1.护理学院神经生物学研究所、2.淮河临床学院、3.药学院,河南 开封 475004
Author(s):
HUO Fei1TANG Nai-fu1 FAN Yuan-yuan1 LIU Shi-meng2 ZHANG Ying2 LIANG Hong-xia1 HU Guo-qiang3 LIU Bin1
1.Institute of Neurobiology, College of Nursing, 2.Huaihe Clinical College, 3.College of Pharmacy, Henan University, Kaifeng Henan 475004, China
关键词:
MMC-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9.40 μmol·L-1 左氧氟沙星盐酸盐作用于SMMC-7721 细胞24 h的IC50值为735.10 μmol·L-1M18作用于骨髓间充质干细胞24 h的IC50值为38.96 μmol·L-1
Keywords:
fluoroquinolones schiff base hepatocarcinoma cells cell proliferation apoptosis mitochondrial membrane potential p53
分类号:
R329. 25; R735. 702. 2; R979. 1
文献标志码:
A
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4~32 μmol·L-1的浓度范围内能明显抑制MMC-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9.40 μmol·L-1; 左氧氟沙星盐酸盐作用于SMMC-7721 细胞24 h的IC50值为735.10 μmol·L-1,M18作用于骨髓间充质干细胞24 h的IC50值为38.96 μmol·L-1; 不同浓度M18 作用人肝癌SMMC-7721 细胞24 h,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。
Abstract:
Aim To study the effect of(S)-1, 8-(2-methyl phosphate ethoxy)-6-fluorine-7-(4-methyl- piperazine-1-base)-3-[S-benzyls-based-4-(for nitrobenzene 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. Methods 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 determined using Hoechst 33258 fluorescence staining and TUNEL method. Mitochondrial membrane potential(△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(4~32 μmol·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 9.40 μmol·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 735.10 μmol·L-1. Treatment of SMMC-7721cells with different concentrations of M18 for 24 h increased the percentage of the apoptosis cells(P<0.05)and decreased the mitochondrial membrane potential. In addition, 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 mitochondrial compartment. Conclusion The mitochondrial-dependent pathways are involved in M18 induction of apoptosis of SMMC-7721 cells.

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备注/Memo

备注/Memo:
收稿日期:2015-01-25,修回日期:2015-03-20 基金项目:国家自然科学基金资助项目(No 21072045); 河南省科技厅科技攻关重点项目(No 112102310307) 作者简介:霍 菲(1990-),女,硕士生,研究方向:肿瘤分子药理学,E-mail: 805767095@qq.com; 刘 彬(1959-),男,硕士,教授,硕士生导师,研究方向: 肿瘤分子生物学,通讯作者,Tel: 0371-23880399,E-mail: lbgood5912@sina.com
更新日期/Last Update: 1900-01-01