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PARP抑制剂对非小细胞肺癌A549及H460细胞增殖及凋亡的影响

Effect of PARP inhibitor PJ34 on cell proliferation and apoptosis of non-small cell lung cancer cell line A549,NCI-H460
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摘要 目的:探讨PARP抑制剂PJ34体外对非小细胞肺癌的增殖及凋亡影响。方法:采用MTT法检测PARP抑制剂PJ34对非小细胞肺癌A549、NCI-H460细胞的增殖抑制作用;Hoechst33342荧光染色法观察PJ34诱导的细胞凋亡;流式细胞术检测PJ34作用后细胞周期变化及凋亡情况。结果:在1.25-20μg/ml浓度范围内,PJ34抑制A549、NCI-H460细胞增殖,且具有浓度和时间依赖性。荧光显微镜下观察到PJ34处理后细胞出现凋亡的形态学变化如核固缩、体积缩小等。细胞周期分析PJ34能将细胞阻滞于细胞周期中G0/G1期。Annxin V-FITC/PI双染流式细胞分析发现PJ34作用后细胞凋亡比例明显增加(P<0.01)。结论:PARP抑制剂PJ34能够抑制非小细胞肺癌A549、NCI-H460细胞增殖,引起细胞周期阻滞、诱导细胞凋亡。 Objective:To investigate the effects of PARP inhibitor PJ34 in vitro on the proliferation and apoptosis of non - small cell lung cancer cell hnes A549, NCI - H460. Methods: The inhibition rates of A549 and H460 ceils exposed to PJ34 were evaluated by MTT method. The morphological changes of apoptosis induced by PJ34 were observed by Hoechst33342 fluorescence staining under the fluorescence microscope. Cell cycle and apoptosis changes of the cell lines treated by PJ34 was detected by flow cytometry. Results :The MTr assay showed PJ34 had significantly antiproliferative effects with a dose and time - dependent way at the concentration ranged from 1.25 to 20μg/ml. Typical apoptotic morphologic changes were observed by fluorescence microscope, such as nuclear condensation and chro- matin condensation. Flow cytometry assay showed that cell cycle was arrested at the G0/GI phase, Annexin V - FIT(I/ PI double staining flow cytometry analysis showed that the apoptosis was significantly increased after PJ34 treatment ( P 〈 0.05 ). Conclusion: PARP inhibitor PJ34 can inhibit non - small cell lung cancer A549, H460 cell proliferation, and cause cycle arrest and induce apoptosis.
作者 马强 郝吉庆
出处 《现代肿瘤医学》 CAS 2013年第4期737-740,共4页 Journal of Modern Oncology
关键词 聚ADP核糖聚合酶类 非小细胞肺癌 细胞增殖 凋亡 PARP non- small cell lung cancer cell proliferation apoptosis
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参考文献12

  • 1Herceg Z, Wang ZQ. Functions of poly ( ADP - ribose ) po|ymerase (PARP) in DNA repair genomie integrity and celldeath[ J]. Murat Res ,2001,477(1/2) :97 - 110.
  • 2Btirkle A. Poly ( APD - ribosyl ) ation, a DNA damage - driven protein modification and regulator of genomie instability[J]. Canc- er Lett,2001,163( 1 ) :1 -5.
  • 3Javle M,Curtin NJ. The role of PARP in DNA repair and its thera- peutic exploriation [ J ]. Br J Cancer,2011,105 ( 8 ) : 1114 - 1 122.
  • 4Calabrese CR, Almassy R, Barton S. et al. Anticancer chemosen- sitization and radiosensltization by the novel poly (ADP- ribose) polymerase- 1 inhibitor AG14361 [J]. J Nail Cancer Inst,2007, 96(1) :56 -67.
  • 5Smith LM,Willmore E, Austin CA, et al. The novel (ADP - Ri- bose) polymerase inhibitor, AG14361, sensitizes cells topoisomer- ase I poisons by increasing the persistence of DNA strand breaks [J]. Clin Cancer Res,2005,11 (23) :8449 -8457.
  • 6Zaremba T. Curtin NJ. PARP inhibitor development for systemic cancer targeting[J]. Anticancer Agents Med Chem,2007,7 (5) : 515 -523.
  • 7Quiles - Perez R, Munoz - Gamez JA, Ruiz - Extremera A, etal. Inhibition of poly adenosine diphosphate - ribose polymerase de- creases hepatocellu|ar carcinoma growth by modulation of tumor - related gene expression [ J ]. Hepatology ,2010,51 ( 1 ) :255 - 266.
  • 8Gangopadhyay NN, Luketich JD, Opest A, et al Inhibition of poly ( ADP - ribose) polymerase (PARP) induces apoptosis in lung cancer cell lines[ J ] Cancer Invest ,2011,29(9) :608 - 616.
  • 9周欣,黄志勇,陈孝平,黄胜辉.PARP-1抑制剂PJ34对人肝癌细胞株HepG2的抑制作用[J].世界华人消化杂志,2007,15(16):1806-1809. 被引量:7
  • 10郑亚东,彭飞,徐西强,虞冀哲,吴华.PARP-1抑制剂对骨肉瘤细胞增殖及凋亡的影响[J].骨科,2011,2(1):13-16. 被引量:4

二级参考文献24

  • 1黄胜辉,黄志勇.PARP-1:一个肿瘤治疗的新靶点[J].世界华人消化杂志,2006,14(9):841-847. 被引量:11
  • 2王志强,黄志勇,陈孝平,张志发.人肝癌组织中PARP-1的表达与生物学特征的关系[J].世界华人消化杂志,2006,14(20):1995-1998. 被引量:6
  • 3Haince JF,Rouleau M,Hendzel MJ.Masson JY,Poirier GG.Targeting poly(ADP-ribosyl)ation:a promising approach in cancer therapy.Trends Mol Med 2005;11:456-463
  • 4http://www.eddn.org/clinicalTr_caResUK.html
  • 5Tentori L,Leonetti C,Scarsella M,Vergati M,Xu W,Calvin D,Morgan L,Tang Z,Woznizk K,Alemu C,Hoover R,Lapidus R,Zhang J,Graziani G.Brain distribution and efficacy as chemosensitizer of an oral formulation of PARP-1 inhibitor GPI 15427 in experimental models of CNS tumors.Int J Oncol 2005;26:415-422
  • 6Dandri M,Burda MR,Burkle A,Zuckerman DM,Will H,Rogler CE,Greten H,Petersen J.Increase in de novo HBV DNA integrations in response to oxidative DNA damage or inhibition of poly (ADPribosyl)ation.Hepatology 2002;35:217-223
  • 7Farmer H,McCabe N,Lord CJ,Tutt AN,Johnson DA,Richardson TB,Santarosa M,Dillon KJ,Hickson I,Knights C,Martin NM,Jackson SP,Smith GC,Ashworth A.Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.Nature 2005;434:917-921
  • 8Nozaki T,Fujihara H,Watanabe M,Tsutsumi M,Nakamoto K,Kusuoka O,Kamada N,Suzuki H,Nakagama H,Sugimura T,Masutani M.Parp-1 deficiency implicated in colon and liver tumorigenesis induced by azoxymethane.Cancer Sci 2003;94:497-500
  • 9Nomura F,Yaguchi M,Togawa A,Miyazaki M,Isobe K,Miyake M,Noda M,Nakai T.Enhancement of poly-adenosine diphosphate-ribosylation in human hepatocellular carcinoma.J Gastroenterol Hepatol 2000;15:529-535
  • 10Yu SW,Wang H,Poitras MF,Coombs C,Bowers WJ,Federoff HJ,Poirier GG,Dawson TM,Dawson VL.Mediation of poly(ADP-ribose)polymerase-1dependent cell death by apoptosis-inducing factor.Science 2002;297:259-263

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