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PHA-767491联合TRAIL抑制肝癌细胞Bel-7404增殖 被引量：1

Combination of PHA-767491 with TRAIL Inhibits Proliferation of Hepatocellular Carcinoma Bel-7404 Cells
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摘要 将小分子抗癌药物PHA-767491和携带TRAIL基因的非复制型腺病毒(Ad-TRAIL)共同作用于肝癌细胞Bel-7404,探讨PHA-767491联合TRAIL蛋白对肝癌细胞增殖的协同抑制作用及其作用机理.MTT法检测细胞存活率,Hoechst 33342荧光检测细胞凋亡现象和流式细胞仪检测细胞凋亡水平.结果表明,PHA-767491联合Ad-TRAIL抑制Bel-7404细胞增殖的能力显著优于单一用药.Western印迹进一步分析蛋白表达水平显示,PHA-767491可以通过下调抗凋亡蛋白Mcl-1和Xiap的表达,从而显著增强TRAIL蛋白诱导Bel-7404细胞凋亡的能力;PHA-767491联合AdTRAIL处理Bel-7404细胞后,不仅Bel-7404细胞凋亡水平显著增加,并且伴随着PARP和Caspase3的大量剪切.本研究证实,PHA-767491和TRAIL的联合使用对抑制肝癌细胞Bel-7404增殖表现出了显著的协同效应,为今后癌症药物的联合治疗提供了新的思路. To explore the coordinating repression to hepatocellular carcinoma cell proliferation by PHA- 767491 combining TRAIL and the inhibiting mechanism, small molecule anti-cancer drug PHA- 767491 and replication-deficient adenoviral vector carrying TRAIL （Ad-TRAIL） were used jointly to work on Bel- 7404 cell. By testting cell survival rate by MTT and observing apoptosis phenomenon via Hoechst 33342 fluorescence staining and apoptosis level by flow cytometry, 767491 with Ad-TRAIL promoted the growth inhibition of. the resuhs showed that combining PHA- Bel-7404 cell compared with either PHA- 767491 or Ad-TRAIL alone. Western blots analysis showed that PHA-767491 enhanced to induce apoptosis of TRAIL by down-regulating Mcl-1 and Xiap expression; PHA-767491 combined with Ad- TRAIL induced remarkable apoptosis and cleavage of caspase 3 and PARP in Bel-7404 cells. In conclusion, combination therapy of PHA-767491 and TRAIL exerted a synergistic anti-tumor effect on Bel-7404 cells, it will provide a new idea for combined treatment of cancer.
作者 李伟 李华美 沈红强 楼金吐 彭朝阳 董敖 尚世强
机构地区 浙江大学医学院附属儿童医院
出处 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2013年第10期941-947,共7页 Chinese Journal of Biochemistry and Molecular Biology
基金 浙江省医药卫生一般计划项目(No.2009B097) 浙江省自然科学基金项目(No.Y2100891)~~
关键词 PHA-767491 TRAIL 协同效应 凋亡 BEL-7404 PHA-767491 TRAIL synergistic effect apoptosis Bel-7404
分类号 Q78 [生物学—分子生物学]
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参考文献20

  • 1李伟,田雪君,刘立,钱程.huCdc7激酶及其与肿瘤的关系[J].生物化学与生物物理进展,2009,36(7):810-816. 被引量：5
  • 2Vanotti E, Amici R, Bargiotti A, et al. Cdc7kinase inhibitors: pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships[ J]. J Med Chem, 2008, 51 (3) : 487-501.
  • 3Montagnoli A, Valsasina B, Croci V, et al. A Cde7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity[ J]. Nat Chem Biol,2008,4(6) :357 -365.
  • 4李伟,张静,胡徐庞,魏旭斌,刘立,钱程.PHA-767491抑制多种肿瘤细胞生长[J].中国生物化学与分子生物学报,2010,26(5):455-461. 被引量：5
  • 5Natoni A, Murillo LS, Kliszczak AE, et al. Mechanisms of action of a dual Cdc7/Cdk9 kinasc inhibitor against quiescent and proliferating C LL ceils [ J ]. Mol Cancer Ther,2011, 10 (9) : 1624- 1634.
  • 6Parajuli B, Shin S J, Kwon SH, et al. The synergistic apoptotic interaction of indole-3- carbinol and genistein with TRAIL on endometrial cancer cells [J]. J Korean Med Sci, 2013, 28(4) : 527-533.
  • 7Zhang H, Sui A, Wang Z, et al. Adenovirus-mediated TRAIL expression and downregulation of Bcl-2 expression suppresses non-small cell lung cancer growth in vitro and in vivo [ J ]. Int J Mol Med, 2012,30(2) :358-364.
  • 8Norian LA, Kresowik TP, Rosevear HM, et al. Eradication of metastatic renal cell carcinoma after adenovirus-encoded TNF- related apoptosis-inducing ligand (TRAIL)/CpG immuno therapy [J]. PLoS One, 2012,7(2):e31085.
  • 9Liu Y, Lang F, Xie X, et al. Efficacy of adenovirally expressed soluble TRAIL in human glioma organotypic slice culture and glioma xenografts [ J ] , 2011,24,2 : e1- 21.
  • 10Zhao Y, Li Y, Wang Q, et al. Increased antitumor capability of fiber-modified adenoviral vector armed with TRAIL against bladder cancers [ J ]. Mol Cell Biochem, 2011,353 ( 1-2 ) :93- 99.

二级参考文献45

  • 1Montagnoli A,Valsasina B,Croci V,et al.A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity.Nat Chem Biol,2008,4(6):357～365
  • 2Jackson A L,Pahl P M,Harrison K,et al.Cell cycle regulation of the yeast Cdc7 protein kinase by association with the Dbf4 protein.Mol Cell Biol,1993,13(5):2899～1908
  • 3Montagnoli A,Bosotti R,Villa F,et al.Drfl,a novel regulatory subunit for human Cdc7 kinase.EMBO J,2002,21(12):3171 3181
  • 4Kumagai H,Sato N,Yamada M,et al.A novel growth-and cell cycle-regulated protein,ASK,activates human Cdc7-related kinase and is essential for G1/S transition in mammalian cells.Mol Cell Biol,1999,19(7):5083～5095
  • 5Masai H,Matsui E,You Z,et al.Human Cdc7-related kinase complex.In vitro phospborylation of MCM by concerted actions of Cdks and Cdc7 and that of a criticial threonine residue of Cde7 by Cdks.J Biol Chem,2000,275(37):29042～29052
  • 6Yamada M,Sato N,Taniyama C,et al.A 63 base-pair DNA segment containing a Sp1 site but not a canonical E2F site can confer growth-dependent and E2F-mediated transcriptional stimulation of the human ASK gene encoding the regulatory subunit for human Cdc7-related kinase.J Biol Chem,2002,277(31):27668～27681
  • 7Kim J M,Yamada M,Masai H,et al.Functions of mammalian Cdc7 kinase in initiation/monitoring of DNA replication and development.Mutat Res,2003,532(1～2):29～40
  • 8Ogino K,Takeda T,Matsui E,et al.Bipartite binding of a kinase activator activates Cdc7-related kinase essential for S phase.J Biol Chem,2001,276(33):31376～31387
  • 9Masai H,Arai K.Cdc7 kinase complex:a key regulator in the initiation of DNA replication.J Cell Physiol,2002,190(3):287～296
  • 10Sato N,Sato M,Nakayama M,et al.Cell cycle regulation of chromatin binding and nuclear localization of human Cdc7-ASK kinase complex.Genes Cells,2003,8(5):451～463

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中国生物化学与分子生物学报
2013年 第10期

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