[1]梁红霞,余艺华,王 萌,等.N-甲基环丙沙星氟喹诺酮查尔酮类衍生物对人胰腺癌BxPC-3细胞凋亡和自噬的影响[J].中国药理学通报,2018,(08):1133-1138.[doi:10.3969/j.issn.1001-1978.2018.08.020]
 LIANG Hong-xia,YU Yi-hua,WANG Meng,et al.Effect of N-methylciprofloxacin-based fluoroquinolone-chalcone derivative on apoptosis and autophagy of human pancreatic carcinoma BxPC-3 cells[J].Chinese Pharmacological Bulletin,2018,(08):1133-1138.[doi:10.3969/j.issn.1001-1978.2018.08.020]
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N-甲基环丙沙星氟喹诺酮查尔酮类衍生物对人胰腺癌BxPC-3细胞凋亡和自噬的影响()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2018年08期
页码:
1133-1138
栏目:
论著
出版日期:
2018-08-26

文章信息/Info

Title:
Effect of N-methylciprofloxacin-based fluoroquinolone-chalcone derivative on apoptosis and autophagy of human pancreatic carcinoma BxPC-3 cells
文章编号:
1001-1978(2018)08-1133-06
作者:
梁红霞1余艺华1王 萌1石贞玉1皇甫超申3胡国强2厉永强3刘 彬1
河南大学 1.护理与健康研究所、2.药学院、3.基础医学院,河南 开封 475004
Author(s):
LIANG Hong-xia1 YU Yi-hua1 WANG Meng1 SHI Zhen-yu1 HUANGFU Chao-shen3 HU Guo-qiang2 LI Yong-qiang3 LIU Bin1
1.Institute of Nursing and Health, 2.College of Pharmacy, 3.School of Basic Medical Science, Henan University, Kaifeng Henan 475004, China
关键词:
HGQ7 胰腺癌细胞 细胞增殖 凋亡 自噬 氯喹
Keywords:
HGQ7 pancreatic carcinoma cells cell proliferation apoptosis autophagy chloroquine
分类号:
R329.24; R329.25; R735.902.2; R978.61
DOI:
10.3969/j.issn.1001-1978.2018.08.020
文献标志码:
A
摘要:
目的 研究N-甲基环丙沙星氟喹诺酮查尔酮类衍生物1环丙基-6-氟-7-(4-甲基-哌嗪-1-基)-3-[2-(3,4,5-三甲氧苯甲酰基)-乙烯-1-基]-喹啉-4-(1H)-酮(HGQ7)对人胰腺癌BxPC-3细胞凋亡和自噬的诱导作用。方法 MTT法检测细胞增殖; AnnexinⅤ-FITC/PI双染法和TUNEL法测定细胞凋亡率; 用自噬抑制剂氯喹处理细胞,验证HGQ7对细胞增殖和凋亡的影响; 间接免疫荧光技术和Western blot法检测细胞自噬标志性蛋白LC3的表达。结果 HGQ7对BxPC-3细胞增殖有明显抑制作用,24、48 h的IC50分别为4.952、4.564 μmol·L-1; 各组HGQ7作用24 h后,细胞凋亡率高于对照组(P<0.01); HGQ7处理导致BxPC-3细胞LC3-Ⅱ表达量增加,6~24 h达到最高,之后明显下降; 自噬抑制剂氯喹增强低剂量HGQ7(0.312 5~2.5 μmol·L-1)对BxPC-3细胞的增殖抑制作用,并进一步提高HGQ7(1.25 μmol·L-1)诱导的细胞凋亡率; 而在高剂量HGQ7(5~10 μmol·L-1)处理BxPC-3细胞时,HGQ7联合氯喹组的细胞生长抑制率明显低于HGQ7单独处理组,HGQ7(5 μmol·L-1)联合氯喹组细胞凋亡率则高于HGQ7单独处理组。结论 HGQ7能够明显诱导BxPC-3细胞凋亡和自噬,低剂量HGQ7作用于BxPC-3细胞时,自噬对细胞具有保护作用,高浓度HGQ7作用时,自噬作用则降低细胞增殖率,促进细胞凋亡。
Abstract:
Aim To study the effect of N-methylciprofloxacin-based fluoroquinolone-chalcone derivative 1-cyclopropyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-3-[2-(3,4,5-trimethoxy-benzoyl)-vinyl-1-yl]-quinolin-4(1H)-one(HGQ7)on apoptosis and autophagy of pancreatic carcinoma BxPC-3 cells in vitro.Methods Cell viability was analyzed by MTT assay.Cell apoptosis was determined by flow cytometry(FCM)with Annexin V-FITC conjugated propidium iodide(PI)staining and TUNEL assay, in which chloroquine(CQ, an autophagy inhibitor)was used to inhibit autophagy.The expressions of autophagy marker protein microtubule associated protein 1 light chain 3(LC3)were detected by indirect immunofluorescence and Western blot.Results HGQ7 showed significant proliferation inhibition activity on BxPC-3 cells.IC50 of 24 h and 48 h was 4.952 μmol·L-1 and 4.564 μmol·L-1, respectively.Treatment of BxPC-3 cells with different concentrations of HGQ7 for 24 h increased the percentage of the apoptotic cells(P<0.01).With the increase of time of exposure to HGQ7, the expressions of autophagy-related proteins LC3-Ⅱof BxPC-3 cells increased, reaching peaks during 6~24 h, but decreased afterwards.The autophagy inhibitor CQ further decreased the viability of cells treated by the low dose HGQ7(0.312 5~2.5 μmol·L-1)and increased the percentage of the apoptotic cells.But CQ with high dose HGQ7(5~10 μmol·L-1)reversed the proliferation inhibition and pre-apoptosis activity of HGQ7 on BxPC-3 cells.Conclusions HGQ7 could induce apoptosis and autophagy of BxPC-3 cells.The autophagy might play a protective role in low dose HGQ7 exposure of BxPC-3 cells.But with high dose HGQ7 group, the autophagy may further decrease the viability and increase the percentage of the apoptotic BxPC-3 cells.

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备注/Memo

备注/Memo:
收稿日期:2018-04-13,修回日期:2018-05-11
基金项目:国家自然科学基金资助项目(No 20872028,21072045); 河南省科技厅科技攻关重点项目(No 112102310307); 河南省教育厅科学技术研究重点项目(No 15A310016)
作者简介:梁红霞(1967-),女,高级实验师,研究方向:肿瘤分子药理学,Tel:0371-23880399,E-mail:976201697@qq.com;
厉永强(1977-),男,硕士,讲师,研究方向:肿瘤分子药理学,通讯作者,E-mail:liyongqiang@vip.henu.edu.cn;
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,E-mail:lbgood5912@sina.com
更新日期/Last Update: 2018-07-26