[1]凡 丞,鲁照明,张幸丽,等.食管鳞癌Eca109细胞中PI3K/AKT/mTOR信号通路对LSD1的调控作用*[J].郑州大学学报(医学版),2017,(05):531-535.[doi:10.13705/j.issn.1671-6825.2017.05.004]
 FAN Cheng,LU Zhaoming,ZHANG Xingli,et al.Regulation effects of PI3K/AKT/mTOR signaling pathway on LSD1 in Eca109 cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2017,(05):531-535.[doi:10.13705/j.issn.1671-6825.2017.05.004]
点击复制

食管鳞癌Eca109细胞中PI3K/AKT/mTOR信号通路对LSD1的调控作用*()
分享到:

《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2017年05期
页码:
531-535
栏目:
食管癌研究
出版日期:
2017-09-15

文章信息/Info

Title:
Regulation effects of PI3K/AKT/mTOR signaling pathway on LSD1 in Eca109 cells
作者:
凡 丞鲁照明张幸丽田 菲白一汝赵 琦彭柯峥刘宏民侯桂琴#
郑州大学药学院 郑州 450001
Author(s):
FAN Cheng LU Zhaoming ZHANG Xingli TIAN Fei BAI Yiru ZHAO Qi PENG Kezheng LIU Hongmin HOU Guiqin
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001
关键词:
食管鳞癌 PI3K/AKT/mTOR通路 LSD1 H3K4me2
Keywords:
esophageal squamous cell carcinoma PI3K/AKT/mTOR signaling pathway LSD1 H3K4me2
分类号:
R735.1
DOI:
10.13705/j.issn.1671-6825.2017.05.004
摘要:
目的:探讨食管鳞癌Eca109细胞中PI3K/AKT/mTOR信号通路对LSD1的调控作用。方法:用不同浓度的PI3K/Akt/mTOR信号通路抑制剂LY294002(0.5、1.0、5.0、10.0、20.0和50.0 μmol/L)、RAD001(0.05、0.50、5.00、10.00、20.00和50.00 μmol/L)分别处理Eca109细胞24、48 h,采用CCK-8实验检测细胞增殖; 然后分别用0、10、20 μmol/L LY294002或RAD001处理Eca109细胞24 h或20 μmol/L LY294002或RAD001处理不同时间(0~72 h),采用Western blot检测PI3K/Akt/mTOR信号通路因子、LSD1及组蛋白H3K4me2表达的变化。结果:LY294002、RAD001处理后,食管鳞癌细胞增殖受抑,且随浓度的增加,抑制作用有增强的趋势(P<0.05); LY294002抑制Eca109细胞中p-p70S6K的表达,上调Raptor、Rictor、p-Akt(Ser473)以及组蛋白H3K4me2的表达; 而RAD001抑制了Raptor、Rictor、p-p70S6K表达,增加p-Akt(Ser473)的表达,并且下调LSD1表达,上调组蛋白H3K4me2的表达(P<0.05)。结论:PI3K/AKT/mTOR信号通路对LSD1存在调控作用。
Abstract:
Aim: To explore the regulation effects of PI3K/AKT/mTOR signaling pathway on LSD1 in esophageal squamous cell carcinoma(ESCC)Eca109 cells.Methods: Eca109 cells were treated with PI3K/AKT/mTOR signaling pathway inhibitor LY294002 or RAD001 with different concentrations for 24, 48 h, then the proliferation of cells was detected by CCK-8 assay. Eca109 cells were treated with LY294002 or RAD001 with different concentration for 24 h,or treated with LY294002 or RAD001 at the same concentration for different time,then the expressions of proteins in PI3K/AKT/mTOR signaling pathway, LSD1 and histone H3K4me2 were detected by Western blot, respectively.Results: The proliferation of Eca109 cells was significantly inhibited by LY294002 or RAD001, and the inhibition effects increased along with the increase of the concentration(P<0.05); LY294002 inhibited the expression of p-p70S6K and promoted the expressions of Raptor, Rictor, p-Akt(Ser473)and histone H3K4me2; while RAD001 inhibited the expressions of Raptor, Rictor, p-p70S6K, up-regulated the expressions of p-Akt(Ser473)and histone H3K4me2, and down-regulated that of LSD1(P<0.05).Conclusion: The PI3K/AKT/mTOR signaling pathway has regulation effects on LSD1.

参考文献/References:

[1] CHEN J,KWONG DL,CAO T,et al.Esophageal squamous cell carcinoma(ESCC):advance in genomics and molecular genetics[J].Dis Esophagus,2015,28(1):84
[2] FALKENBERG KJ,JOHNSTONE RW.Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders[J].Nat Rev Drug Discov,2014,13(9):673
[3] SUN G,ALZAYADY K,STEWART R,et al.Histonedemethylase LSD1 regulates neural stem cell proliferation[J].Mol Cell Biol,2010,30(8):1997
[4] PRESNEAU N,SHALABY A,IDOWU B,et al.Potential therapeutic targets for chordoma: PI3K/AKT/TSC1/TSC2/mTOR pathway[J].Br J Cancer,2009,100(9):1406
[5] BURG JM,GONZALEZ JJ,MAKSIMCHUK KR,et al.Lysine-specific demethylase 1A(KDM1A/LSD1):product recognition and kinetic analysis of full-length histones[J].Biochemistry,2016,55(11):1652
[6] 翟曜耀,刘晓霞,赵越.赖氨酸特异性组蛋白去甲基化酶1作用机制及其生物学功能的研究进展[J].生命科学,2012,24(1):7
[7] LI Y,TIAN X,SUI CG,et al.Interference of lysine-specific demethylase 1 inhibits cellular invasion and proliferation in vivo in gastric cancer MKN-28 cells[J].Biomed Pharmacother,2016,82:498
[8] DUFFY MJ,MCGOWAN PM,GALLAGHER WM.Cancer invasion and metastasis: changing views[J].J Pathol,2008,214(3):283
[9] TOKER A.Achieving specificity in Akt signaling in cancer[J].Adv Biol Regul,2012,52(1):78
[10]FOLLO MY,MANZOLI L,POLI A,et al.PLC and PI3K/Akt/mTOR signalling in disease and cancer[J].Adv Biol Regul,2015,57:10
[11]LIN Y,KANG T,ZHOU BP.Doxorubicin enhances Snail/LSD1-mediated PTEN suppression in a PARP1-dependent manner[J].Cell Cycle,2014,13(11):1708
[12]YOKOYAMA A,TAKEZAWA S,SCHÜLE R,et al.Transrepressive function of TLX requires the histone demethylase LSD1[J].Mol Cell Biol,2008,28(12):3995
[13]YOKOYAMA A,IGARASHI K,SATO T,et al.Identification of myelin transcription factor 1(MyT1)as a subunit of the neural cell type-specific lysine-specific demethylase 1(LSD1)complex[J].J Biol Chem,2014,289(26):18152
[14]SHAO G,WANG J,LI Y,et al.Lysine-specific demethylase 1 mediates epidermal growth factor signaling to promote cell migration in ovarian cancer cells[J].Sci Rep,2015,5:15344
[15] DJUKOM C, PORRO LJ, MRAZEK A, et al. Dual inhibition of PI3K and mTOR signaling pathways decreases human pancreatic neuroendocrine tumor metastatic progression[J]. Pancreas, 2014, 43(1):88
[16]WERZOWA J,CEJKA D,FUEREDER T,et al.Suppression of mTOR complex 2-dependent AKT phosphorylation in melanoma cells by combined treatment with rapamycin and LY294002[J].Br J Dermatol,2009,160(5):955
[17]EFEYAN A,SABATINI DM.mTOR and cancer: many loops in one pathway[J].Curr Opin Cell Biol,2010,22(2):169

相似文献/References:

[1]魏攀,李杰,王莉莉,等.转染杜氏盐藻1433基因对食管鳞癌EC9706细胞Bcl2和Caspase9蛋白表达的影响*[J].郑州大学学报(医学版),2010,(01):4.
 WEI Pan,LI Jie,WANG Lili,et al.Expression of Bcl2 and Caspase9 proteins of EC9706 cell transfected 1433 gene of Dunaliella salina[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2010,(05):4.
[2]郑乃刚)),阎爱华),吴景兰),等.食管鳞癌的肿瘤干细胞标志[J].郑州大学学报(医学版),2010,(01):27.
 ZHENG Naigang),YAN Aihua),WU Jinglan),et al.Cancer stem cell biomarker in human esophageal squamous cell carcinoma tissue and Eca109 and EC9706 cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2010,(05):27.
[3]侯桂琴),贝维娟),杨帅),等.食管鳞癌细胞中PTEN基因表达水平及突变位点分析*[J].郑州大学学报(医学版),2013,(05):577.
 HOU Guiqin),BEI Weijuan),YANG Shuai),et al.Expression and mutation sites analysis of PTEN gene in esophageal squamous cell carcinoma cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2013,(05):577.
[4]卢红△,王建军,周芳.食管鳞癌组织中磷酸化表皮生长因子受体和Akt蛋白的表达*[J].郑州大学学报(医学版),2015,(01):5.
 LU Hong,WANG Jianjun,ZHOU Fang.Expressions of pEGFR and pAkt proteins in esophageal squamous cell carcinoma tissue[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2015,(05):5.
[5]吕 双),宋 昕),赵学科),等.食管鳞癌肿瘤最大长径与浸润深度(T分期)的关系*[J].郑州大学学报(医学版),2017,(05):522.[doi:10.13705/j.issn.1671-6825.2017.05.002]
 LYU Shuang),SONG Xin),ZHAO Xueke),et al.Relationship between the maximum tumor length and invasion depth(T Stage)in esophageal squamous cell carcinoma[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2017,(05):522.[doi:10.13705/j.issn.1671-6825.2017.05.002]
[6]张幸丽,侯桂琴,凡 丞,等.食管鳞癌细胞中LSD1通过与Notch靶基因启动子结合调控Notch通路相关蛋白表达*[J].郑州大学学报(医学版),2017,(06):672.[doi:10.13705/j.issn.1671-6825.2017.06.003]
 ZHANG Xingli,HOU Guiqin,FAN Cheng,et al.LSD1 regulates expression of related proteins of Notch pathway through combining promotor of target gene of Notch in esophageal squamous cell carcinoma cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2017,(05):672.[doi:10.13705/j.issn.1671-6825.2017.06.003]
[7]张 乐),李庆华),杨 璐),等.DZNep对裸鼠食管鳞癌移植瘤生长的抑制作用[J].郑州大学学报(医学版),2018,(01):17.[doi:10.13705/j.issn.1671-6825.2017.02.060]
 ZHANG Le),LI Qinghua),YANG Lu),et al.Inhibition effects of DZNep on growth of esophageal squamous cell carcinoma xenograft in nude mice[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2018,(05):17.[doi:10.13705/j.issn.1671-6825.2017.02.060]
[8]刘怡文,孙 蔚,齐义军,等.食管鳞癌组织中GSK3β表达的临床意义[J].郑州大学学报(医学版),2018,(01):21.[doi:10.13705/j.issn.1671-6825.2016.12.060]
 LIU Yiwen,SUN Wei,QI Yijun,et al.Clinical significance of GSK3β expression in esophageal squamous cell carcinoma tissue[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2018,(05):21.[doi:10.13705/j.issn.1671-6825.2016.12.060]
[9]陈丹杰,孟祥瑞,刘 灿,等.食管鳞癌淋巴结包膜外侵犯对预后相关因素的影响[J].郑州大学学报(医学版),2018,(03):276.[doi:10.13705/j.issn.1671-6825.2017.09.068]
 CHEN Danjie,MENG Xiangrui,LIU Can,et al.The influence of lymph nodes extranodal extension of esophageal squamous cell carcinoma on the prognostic factors[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2018,(05):276.[doi:10.13705/j.issn.1671-6825.2017.09.068]
[10]韩少华),万里新),李秀敏),等.食管鳞癌组织中E-cadherin蛋白表达及对术后预后的影响[J].郑州大学学报(医学版),2019,(02):182.[doi:10.13705/j.issn.1671-6825.2018.12.083]
 HAN Shaohua),WAN Lixin),LI Xiumin),et al.Impact of E-cadherin protein expression in esophageal squamous cell carcinoma tissue on postoperation prognosis[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2019,(05):182.[doi:10.13705/j.issn.1671-6825.2018.12.083]

备注/Memo

备注/Memo:
*国家自然科学基金重点项目 81430085; 河南省基础与前沿技术研究计划项目 162300410122
#通信作者,女,1977年6月生,博士,副教授,研究方向:肿瘤细胞分子生物学,E-mail:hougq@zzu.edu.cn
更新日期/Last Update: 2017-09-20