You Position: Home > Paper
BRD4 inhibitor JQ1 inhibits viability of hepatocellular carcinoma cells
( views:46, downloads:0 )
- Author:
- No author available
- Journal Title:
- World Chinese Journal of Digestology
- Issue:
- 10
- DOI:
- 10.11569/wcjd.v24.i10.1501
- Key Word:
- 溴结构域蛋白4;JQ1;肝细胞肝癌;增殖;凋亡;C-myc;甲苯磺酸索拉非尼片;Bromodomain-containing protein 4;JQ1;Hepatocellular carcinoma;Proliferation;Apoptosis;C-myc;Sorafenib
Abstract： 目的:探讨溴结构域蛋白4(bromodomain-containing protein 4,BRD4)抑制剂JQ1对两种不同肝癌细胞系增殖、凋亡的影响.方法:用BRD4抑制剂JQl处理HepG2,Bel-7402细胞株,磺酰罗丹明B(sulforhodamine B,SRB)染色检测细胞活力;EdU(5-ethynyl-2'-deoxyuridine)嵌入和Hoechst 33342染色法检测细胞增殖;以流式细胞术和AnnexinV-FITC/PI双染法分别分析细胞周期、细胞凋亡;最后用Western blot法观察JQl介导抗增殖作用主要下调蛋白C-myc在蛋白水平上的变化,进一步验证JQ1抑制肝癌细胞增殖的作用.同时探讨JQ1与目前肝癌细胞治疗药物甲苯磺酸索拉非尼片对肝癌细胞的比较和联合作用.结果:BRD4抑制剂JQ1可以以剂量依赖的方式显著抑制HCC细胞系:HepG2细胞和Bel-7402细胞的活力,具体表现为:抑制其细胞增殖;Annexin V-FITC/PI双染法分析发现能促进其凋亡;同时C-myc蛋白表达的也被显著抑制.与JQ1、索拉非尼片单药应用相比,小剂量的JQ1与索拉非尼片联合应用,HCC细胞的生长抑制率增加,凋亡率也增加,提示BR D4抑制剂JQ1联合索拉非尼片对细胞生长的抑制作用要强于JQ1或索拉非尼片单独用药.结论:BRD4抑制剂JQ1可能是一种潜在的可治疗肝细胞癌的新型药物.
- [1]仝营营,丁文评,张莲,等.溴结构域蛋白4在肿瘤中的研究进展[J].2015,(1).
- [2]刘忠,杨飞,程吉,等.BRD4抑制剂对鼻咽癌CNE-2细胞增殖、凋亡和侵袭的影响[J].2015,(6).
- [3]Jerome Byam,John Renz,J. Michael Millis.Liver transplantation for hepatocellular carcinoma[J].2013,(1).
- [4]Wu, Yuntao,Li, Zichong,Guo, Jia,etc.The BET bromodomain inhibitor JQ1 activates HIV latency through antagonizing Brd4 inhibition of Tat-transactivation[J].2013,41(1).
- [5]Cheng,Z.,Gong,Y.,Ma,Y.,etc.Inhibition of BET bromodomain targets genetically diverse glioblastoma[J].2013,19(7).
- [6]Mertz, J.A.,Conery, A.R.,Bryant, B.M.,etc.Targeting MYC dependence in cancer by inhibiting BET bromodomains[J].2011,108(40).
- [7]Bravi,F.,Bosetti,C.,Tavani,A.,etc.Coffee reduces risk for hepatocellular carcinoma: An updated meta-analysis[J].2013,11(11).
- [8]Susanne, Muller,Panagis, Filippakopoulos,Stefan, Knapp.Bromodomains as therapeutic targets.[J].2011,13.
- [9]El Serag HB.Hepatocellular carcinoma.[J].2011,365(12).
- [10]Wenhui Qiao,Feng Yu,Lupeng Wu,etc.Surgical outcomes of hepatocellular carcinoma with biliary tumor thrombus: a systematic review[J].2016,(1).
- [11]Kouzarides,T.,Dawson,M.A.,Huntly,B.J.P..Targeting epigenetic readers in cancer[J].2012,367(7).
- [12]Shi, J.,Kung, A.L.,Jacobs, H.M.,etc.BET bromodomain inhibition as a therapeutic strategy to target c-Myc[J].2011,146(6).
- [13]Hato, Tai,Zhu, Andrew X.,Duda, Dan G..Rationally combining anti-VEGF therapy with checkpoint inhibitors in hepatocellular carcinoma[J].2016,8(3).
- [14]Franceschet, Irene,Cazzagon, Nora,Del Ross, Teresa,etc.Primary sclerosing cholangitis associated with inflammatory bowel disease: an observational study in a Southern Europe population focusing on new therapeutic options[J].2016,28(5).
- [15]Jeng, Mark Y.,Ali, Ibraheem,Ott, Melanie.Manipulation of the host protein acetylation network by human immunodeficiency virus type 1[J].2015,50(1).
- [16]Marie-Magdelaine, Coudé,Thorsten, Braun,Jeannig, Berrou,etc.BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells.[J].2015,6.
- [17]Crowe, Brandon L.,Larue, Ross C.,Yuan, Chunhua,etc.Structure of the Brd4 ET domain bound to a C-terminal motif from gamma-retroviral integrases reveals a conserved mechanism of interaction[J].2016,113(8).
- [18]Panagis Filippakopoulos,Jun Qi,Sarah Picaud,etc.Selective inhibition of BET bromodomains[J].2010,468(Dec.23/30 TN.7327).
- [19]Knox, Jennifer,Brierley, James,Ng, Sylvia,etc.Phase 1 Trial of Sorafenib and Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma[J].2016,94(3).
- [20]Johannes Zuber,Junwei Shi,Eric Wang,etc.RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia[J].2011,478(Oct.27 TN.7370).