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Inhibitory effect of peptide nucleic acid on the growth of colorectal cancer LS-174T cells

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Author:: No author available

Journal Title:: WORLD CHINESE JOURNAL OF DIGESTOLOGY

Issue:: 11

DOI:: 10.3969/j.issn.1009-3079.2008.11.008

Key Word:: 肽核酸;端粒酶;转染;大肠癌

Abstract：目的:探讨肽核酸(peptide or polyamide nucleic acid,PNA)对大肠癌细胞端粒酶活性的抑制作用及对大肠癌细胞生长的影响.方法:应用脂质体Lipfectamine TM介导不同浓度(25,50,100,200,400 nmol/L)PNA-DNA杂交混合物转染LS-174T细胞.通过细胞克隆生长抑制试验来测定PNA对细胞生长的最佳抑制剂量;选用最佳抑制剂量PNA转染LS-174T细胞,同时设置脂质体组(Lipfectamine TM)组和空白对照组,观察克隆形成率、细胞形态及群体生长差异.结果:PNA对LS-174T细胞最佳抑制浓度为200 nmol/L.PNA实验组端粒酶活性和克隆形成率明显低于脂质体组和空白对照组(0.003±0.001 vs 2.334±0.025,2.528±0.032,P<0.01;5.20% vs 45.45%,47.13%,P<0.01).PNA组癌细胞生长出现典型形态学改变,细胞变圆、胞膜皱缩、细胞核边集于核膜,通过群体生长曲线,转染后11d出现抑制作用,15、17d抑制作用最显著.结论:体外试验中PNA对大肠癌LS-174T细胞生长有明显的抑制作用.其作用机制可能是PNA对大肠癌细胞端粒酶活性的抑制.

Reference

[1]Ming LI,Jin Gu.Changing patterns of colorectal cancer in China over a period of 20 years[J].2005,(30).
[2]Ya-Li Zhang,Zhen-Su Zhang,Ba-Ping Wu,etc.Early diagnosis for colorectal cancer in China[J].2002,(1).
[3]M Vidaurreta,ML Maestro,S Rafael,etc.Telomerase activity in colorectal cancer, prognostic factor and implications in the microsatellite instability pathway[J].2007,(28).
[4]Xi-Shan Wang,Kuan Wang,XUE Li,etc.Effects of phosphorothioate anti-sense oligodeoxynucleotides on colorectal cancer cell growth and telomerase activity[J].2004,(23).
[5]王雪峰,陈永井,王勤,等.转染人BTLA基因细胞株的建立及其生物学功能的初步研究[J].2007,(3).
[6]Tonelli R,Pession A.The MYCN oncogene as a specific and selective drug target for peripheral and central nervous system tumors.[J].2005,5(4).
[7]Teh HF,Lieu XH,Su X,etc.Enzyme-based colorimetric detection of nucleic acids using peptide nucleic acid-immobilized microwell plates[J].2007,79(18).
[8]F, Sampedro Camarena,G, Cano Serral,F, Sampedro Santaló.Telomerase and telomere dynamics in ageing and cancer: current status and future directions.[J].2007,9(3).
[9]Robert H, Vonderheide.Universal tumor antigens for cancer vaccination: targeting telomerase for immunoprevention.[J].2007,7(39).
[10]Miura K,Komiyama M,Uehara A,etc.Development of artificial restriction DNA cutter composed of Ce(Iv)/EDTA and PNA.[J].2007,26(10).
[11]Nozawa H,Nagawa H,Ohnishi T,etc.Telomerase subunit immunoreactivity and recurrence in colorectal cancer.[J].2006,53(68).
[12]Bender M,Holben WE,Sorensen SJ,etc.Use of a PNA probe to block DNA-mediated PCR product formation in prokaryotic RT-PCR[J].2007,42(5).
[13]David R. Corey,Jiaxin Hu.Inhibiting Gene Expression with Peptide Nucleic Acid (PNA)-Peptide Conjugates That Target Chromosomal DNA[J].2007,46(25).
[14]Roy S,Tanious FA,Wilson WD,etc.High-affinity homologous peptide nucleic acid probes for targeting a quadruplex-forming sequence from a MYC promoter element[J].2007,46(37).
[15]Cameron F E, Platell.Changing patterns of recurrence after treatment for colorectal cancer.[J].2007,22(10).
[16]Alan J. Tackett,Kevin D. Raney,Thomas E. Goodwin,etc.Unwinding of Unnatural Substrates by a DNA Helicase[J].2001,40(2).
[17]P E, Nielsen,M, Egholm,R H, Berg,etc.Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide.[J].1991,254.
[18]Robak T.Therapy of chronic lymphocytic leukaemia with purine nucleoside analogues: facts and controversies.[J].2005,22(12).
[19]Gisselsson D,Calcagnile O.Telomere dysfunction and telomerase activation in cancer - a pathological paradox?[J].2007,118(2).
[20]Wolfe HR,Qin W,Wickstrom E,etc.Tumor-targeting peptide-PNA-peptide chimeras for imaging overexpressed oncogene mRNAs.[J].2005,24(5).
[21]Nakagawa K,Eitsuka T,Miyazawa T.Down-regulation of telomerase activity in DLD-1 human colorectal adenocarcinoma cells by tocotrienol.[J].2006,348(1).
[22]Bukanov NO,Frank-Kamenetskii MD,Demidov VV,etc.PD-loop: a complex of duplex DNA with an oligonucleotide.[J].1998,95(10).
[23]Kurt Berlin,Philipp Schatz,Matthias Schuster,etc.Novel method for high throughput DNA methylation marker evaluation using PNA-probe library hybridization and MALDI-TOF detection[J].2006,34(8).
[24]Gao M,Zhang X,Li B,etc.Effects of CD59 on antitumoral activities of phycocyanin from Spirulina platensis.[J].2005,59(10).
[25]Liang XQ,Qin JF,Zhang Y,etc.Increasing sensitivity to arsenic trioxide-induced apoptosis by altered telomere state.[J].2003,474(2).