[1]刘腾飞,周建康,黄团结,等.MS-275对食管鳞癌KYSE-70细胞存活、细胞周期、凋亡及迁移的影响[J].郑州大学学报(医学版),2018,(05):547-552.[doi:10.13705/j.issn.1671-6825.2018.04.093]
 LIU Tengfei,ZHOU Jiankang,HUANG Tuanjie,et al.Effects of MS-275 on survival,cell cycle,apoptosis and migration of human esophageal squamous cancer KYSE-70 cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2018,(05):547-552.[doi:10.13705/j.issn.1671-6825.2018.04.093]
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MS-275对食管鳞癌KYSE-70细胞存活、细胞周期、凋亡及迁移的影响()
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《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2018年05期
页码:
547-552
栏目:
食管癌研究
出版日期:
2018-09-20

文章信息/Info

Title:
Effects of MS-275 on survival,cell cycle,apoptosis and migration of human esophageal squamous cancer KYSE-70 cells
作者:
刘腾飞周建康黄团结王亚苹周馨魁张 乐张璐玉陈一豪刘红涛关方霞马珊珊
郑州大学生命科学学院 郑州 450001
Author(s):
LIU TengfeiZHOU JiankangHUANG TuanjieWANG YapingZHOU XinkuiZHANG LeZHANG LuyuCHEN Yihao LIU HongtaoGUAN FangxiaMA Shanshan
College of Life Sciences,Zhengzhou University,Zhengzhou 450001
关键词:
MS-275 食管鳞癌 组蛋白去乙酰化酶 PI3K/Akt/mTOR
Keywords:
MS-275 esophageal squamous cancer histone deacetylase PI3K/Akt/mTOR
分类号:
R735.1
DOI:
10.13705/j.issn.1671-6825.2018.04.093
摘要:
目的:观察MS-275对食管鳞癌KYSE-70细胞存活、细胞周期、凋亡以及迁移的影响,并分析其对PI3K/Akt/mTOR信号通路相关蛋白p-Akt1和p-mTOR的影响。方法:采用qRT-PCR和Western blot检测KYSE-70细胞和正常食管上皮Het-1A细胞中HDAC1 mRNA及蛋白的表达; CCK-8法检测不同浓度(0.25、0.50、1.00、2.00、4.00、8.00 μmol/L)MS-275对KYSE-70细胞存活的影响; 以0.00、0.25、0.50、1.00和2.00 μmol/L MS-275处理KYSE-70细胞, 48 h后流式细胞仪检测细胞周期,Annexin V/PI染色检测细胞凋亡,划痕实验检测细胞迁移情况,Western blot 检测细胞中Cyclin D1、Cleaved caspase-3、E-cadherin、p-Akt1和p-mTOR蛋白的表达情况。结果:与Het-1A细胞相比,KYSE-70细胞中HDAC1 mRNA和蛋白表达显著增加(P<0.05); MS-275对KYSE-70细胞存活的影响具有时间和剂量依赖性(P<0.05); 随着MS-275处理浓度的增加, KYSE-70 G0/G1期细胞增加、S期细胞降低,细胞凋亡率提高,划痕愈合率降低(P<0.05)。MS-275可提高Cleaved caspase-3和E-cadherin蛋白的表达,降低Cyclin D1、p-Akt1和p-mTOR蛋白的表达(P<0.05)。结论:MS-275可降低KYSE-70细胞存活率,有效抑制细胞迁移,阻滞细胞于G0/G1期,促进细胞凋亡,其作用可能与PI3K/Akt/mTOR信号通路的抑制有关。
Abstract:
Aim:To investigate the effects of MS-275 on the cell survival, apoptosis,cell cycle and migration of human esophageal squamous cancer KYSE-70 cells and analyze PI3K/Akt/mTOR signaling pathway related protein expression.Methods: The expression levels of HDAC1 mRNA and protein in KYSE-70 cells and normal esophageal epithelial cells(Het-1A)were respectively detected by qRT-PCR and Western blot; the survival of KYSE-70 cells was detected by CCK-8 to determine the optimal time and concentration; KYSE-70 cells were treated with 0.00,0.25,0.50,1.00,2.00 μmol/L MS-275 for 48 h,then the apoptosis and the change of cell cycle were detected by flow cytometry; cell migration ability was detected by cell scratches experiment; Cyclin D1,Cleaved caspase-3,E-cadherin and the key proteins(p-Akt1 and p-mTOR)of PI3K/Akt/mTOR signaling pathway were detected by Western blot.Results:HDAC1 mRNA and protein were overexpressed in KYSE-70 cells(P<0.05)compared with Het-1A cells; CCK-8 assay showed that the survival of KYSE-70 cells were inhibited by MS-275 in a dose-and time-dependent manner(P<0.05); with the increase of the concentration of MS-275, the apoptosis rate of KYSE-70 cells was significantly increased,the proportion of cells in G0/G1 phase was increased,that of S phase cells was decreased,and the number of migrating cells was significantly decreased(P<0.05); the relative contents of Cleaved caspase-3 and E-cadherin protein were increased,but those of Cyclin D1,p-Akt1 and p-mTOR protein were reduced by MS-275(P<0.05).Conclusion:MS-275 can effectively inhibit survival and migration,induce apoptosis,arrest cycle of KYSE-70 cells,which might be related with the inhibition of PI3K/Akt/mTOR signaling pathway.

参考文献/References:

[1] TORRE LA,BRAY F,SIEGEL RL,et al.Global cancer statistics, 2012[J].CA Cancer J Clin,2015,65(2):87
[2] HESS-STUMPP H,BRACKER TU,HENDERSON D.MS-275, a potent orally available inhibitor of histone deacetylases:the development of an anticancer agent[J].Int J Biochem Cell Biol,2007,39(7/8):1388
[3] XIAO W,DONG W,ZHANG C,et al.Effects of the epigenetic drug MS-275 on the release and function of exosome-related immune molecules in hepatocellular carcinoma cells[J].Eur J Med Res,2013,18:61
[4] TRAPANI D,ESPOSITO A,CRISCITIELLO C,et al.Entinostat for the treatment of breast cancer[J].Expert Opin Investig Drugs,2017,26(8):965
[5] ZHU S,DENMAN CJ,COBANOGLU ZS,et al.The narrow-spectrum HDAC inhibitor entinostat enhances NKG2D expression without NK cell toxicity, leading to enhanced recognition of cancer cells[J].Pharm Res,2015,32(3):779
[6] YONG KJ,LI A,OU WB,et al.Targeting SALL4 by entinostat in lung cancer[J].Oncotarget,2016,7(46):75425
[7] PILI R,QUINN DI,HAMMERS HJ,et al.Immunomodulation by entinostat in renal cell carcinoma patients receiving high-dose interleukin 2:a multicenter, single-arm, phase Ⅰ/Ⅱ trial(nci-ctep#7870)[J]. Clin Cancer Res,2017,23(23):7199
[8] ZHANG H,CHEN P,BAI S,et al.The histone deacetylase inhibitor MS-275 induces p21WAF1/Cip1 expression in human Hep3B hepatoma cells[J].Drug Dev Res,2007,68(2):61
[9] ZHU S,HE C,DENG S,et al.MiR-548an, transcriptionally downregulated by HIF1α/HDAC1, suppresses tumorigenesis of pancreatic cancer by targeting vimentin expression[J].Mol Cancer Ther,2016,15(9):2209
[10]WANG LT,LIOU JP,LI YH,et al.A novel classⅠ HDAC inhibitor, MPT0G030, induces cell apoptosis and differentiation in human colorectal cancer cells via HDAC1/PKCδ and E-cadherin[J].Oncotarget,2014,5(14):5651
[11]ZHAO R,HAN C,EISENHAUER E,et al.DNA damage-binding complex recruits HDAC1 to repress Bcl-2 transcription in human ovarian cancer cells[J].Mol Cancer Res,2014,12(3):370
[12]LEE BI,PARK SH,KIM JW,et al.MS-275, a histone deacetylase inhibitor, selectively induces transforming growth factor beta type Ⅱ receptor expression in human breast cancer cells[J].Cancer Res,2001,61(3):931
[13]李鹏坤,肖桂芝,田红,等.组蛋白去乙酰化酶抑制剂恩替诺特[J].现代药物与临床,2015,30(3):341
[14]MANSLMAYER G, KONTUREK P,HEROLD C, et al. Antitumoral efficacy of four histone deacetylase inhibitors in hepatoma in vitro and in vivo[J]. Anticancer Res, 2012, 32(12):5263
[15]VENZA I,VISALLI M,OTERI R,et al.Class Ⅰ-specific histone deacetylase inhibitor MS-275 overrides TRAIL-resistance in melanoma cells by downregulating c-FLIP[J]. Int Immunopharmacol,2014, 21(2):439
[16] ZHANG HY, HEN P, BAI SJ, et al. The histone deacetylase inhibitor MS-275 induces p21WAF1/Cip1 expression in human Hep3B hepatoma cells[J]. Drug Dev Res, 2007, 68(2):61
[17]JORAAN G,LIAO W,SHARMA S. E-cadherin gene re-expression in chronic lymphocytic leukemia cells by HDAC inhibitors[J]. BMC Cancer, 2013,13:88
[18]武强,赵金年,宋卫东.PI3K/Akt/mTOR信号通路在肿瘤的研究进展[J].疾病监测与控制杂志,2013,7(6):346
[19]MASSIHNIA D,PEREZ A,BAZAN V,et al.A headlight on liquid biopsies: a challenging tool for breast cancer management[J].Tumour Biol,2016,37(4):4263

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备注/Memo

备注/Memo:
【基金项目】国家自然科学基金资助项目(81601078,81471306); 河南省高校科技创新团队支持计划(15IRTSTHN022); 河南省科技创新人才计划(154200510008)
【作者简介】关方霞,通信作者,女,1969年2月生,博士,教授,研究方向:生物医学,E-mail:guangfangxia@126.com; 马珊珊,通信作者,女,1984年5月生,博士,副教授,研究方向:生物医学,E-mail:mashanshan84@163.com
更新日期/Last Update: 2018-09-20