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人肽脱甲酰基酶基因pdf与肿瘤细胞生长的相关性 被引量:2

Relevance between Homo sapiens peptide deformylase gene(pdf) and the proliferation of tumor cells
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摘要 目的:研究人肽脱甲酰基酶(HsPDF)基因pdf在不同肿瘤细胞系中的表达情况并探讨该基因与肿瘤细胞生长的相关性。方法:体外培养肿瘤细胞,采用半定量RT-PCR方法检测不同肿瘤细胞系中pdfmRNA的水平;用HsPDF抑制剂Actinonin处理细胞并通过细胞形态学、MTT法、RT-PCR及凝胶电泳等技术检测pdf基因与肿瘤细胞生长的相关性。结果:RT-PCR结果表明,该基因在13种不同来源的人肿瘤细胞系和正常组织中的表达具有显著差异。其中,在Hela、MDA-MB-231、K562等肿瘤细胞系中高表达,而在人正常肺组织中低表达(P<0.001)。体外试验显示,Actinonin可显著地抑制肿瘤细胞的生长,使细胞中pdf基因表达量相应的下降,且呈明显的浓度依赖性;同时,光镜观察结果显示Actinonin对肿瘤细胞有诱导凋亡的作用。结论:pdf是一种广泛分布于不同组织的基因,它与肿瘤细胞的生长增殖间存在着显著的相关性。 Aim: To investigate the expression of the corresponding gene pdf in several tumor cell lines and to find out the relevance between the expressior of pdf gene and the proliferation of tumor cells. Methods: A panel of human cell lines were set up by the generic in vitro culture techs. Semi-quantitative RT-PCR experiment was performed to determine the expression abundance of the target gene in the cell lines. Simultaneously, tumor cells were treated with Actinonin, a HsPDF inhibitor. In succession, the relevance between the target gene and the growth of tumor cells was assessed through a variety of analysis as follows: optical microscope imaging, MTF assay, and semi-quantitative RTPCR. Resutls: Results of RT-PCR operation had indicated that human gene pdf was present in 13 sorts of human cell lines and the normal tissue tested, representing 10 different cell lineages and the mRNA expression abundance showed extremely significant differences (P 〈 0.001). Studies carried out in treatment with Actinonin had indicated that it had a potent inhibition in a dose-dependent manner on pdf gene expression and tumor cell proliferation. Moreover, observations by the optical microscope imaging has primarily suggested that Actinonin might have an apoptosis-inducing effect on tumor cells. Conclusons: Human pdf gene is widely distributed in the various types of tissues and has a notable relevance with the growth and proliferation of tumor cells. Therefore, it's very likely that this human gene could be a new target which plays an important role in occmence and development of human cancers.
出处 《中国药科大学学报》 CAS CSCD 北大核心 2006年第5期474-478,共5页 Journal of China Pharmaceutical University
关键词 人pdf基因 肿瘤细胞 Actinonin 半定量RT-PCR human pdf gene tumor cells Actinonin semi-quantitative RT-PCR
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共引文献11

同被引文献41

  • 1Giglione C, Serero A, Pierre M, et al. Identification of eukaryotic peptide deformylases reveals universality of N-terminal protein processing mechanisms [ J ]. EMBO J, 2000,19 ( 21 ) : 5 916 - 5 929.
  • 2Lee MD, She YH,Soskis MJ,et al. Human mitochondrial peptide deformylase, a new anticaneer target of actinonin-based antibiotics [J]. J Clin Invest,2004,114(8) :1 107 -1 116.
  • 3Serero A, Giglione C, Sardini A, et al. An unusual peptide deformylase features in the human mitochondrial N-terminal methionine excision pathway [ J ]. J Biol Chem,2003,278 ( 52 ) : 52 953 - 52 963.
  • 4萨姆布鲁克J,拉塞尔D.分子克隆实验指南[M].黄培堂,译.3版.北京:科学出版社,2004:68-71.
  • 5Nguyen KT, Hu X, Colton C, et al. Characterization of a human peptide deformylase: implications for antibacterial drug design [ J ]. Biochemistry,2003,42 ( 33 ) :9 952 - 9 958.
  • 6Lee MD,Antczak C,Li Y, et al. A new human peptide deformylase inhibitable by actinonin[ J ]. Biochem Biophys Res Commun, 2003,312(2) :309 -315.
  • 7Xu Y, Lai LT, Gabrilove JL, et al. Antitumor activity of actinonin in vitro and in vivo [ J ]. Clin Cancer Res, 1998,4 ( 1 ) : 171 - 176.
  • 8Xu Y, Scheinberg DA. Elimination of human leukemia by monoclonal antibodies in an athymic nude mouse leukemia model [ J ]. Clin Cancer Res,1995,1(10) :1 179 - I 187.
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