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NF-H基因参与K562/A02细胞多药耐药机制形成的研究 被引量:5

Identification of differentially expressed genes involved in multidrug resistance in K562/A02 by cDNA microarray
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摘要 目的 分析K5 6 2 /A0 2细胞多药耐药性 (MDR)分子机制 ,寻找可能参与K5 6 2 /A0 2细胞耐药机制的新基因。方法 通过长期逐步增加K5 6 2细胞培养液中阿霉素 (ADM)的浓度 ,诱导出多药耐药细胞株K5 6 2 /A0 2 ,利用cDNAmicroarray比较K5 6 2和K5 6 2 /A0 2基因表达的差别 ,从中选择NF H基因进行RT PCR和免疫细胞化学验证 ,并利用反义核酸技术和细胞内ADM浓度的测定 ,进一步验证该基因与K5 6 2 /A0 2细胞多药耐药的关系。结果 通过比较发现 ,有 12个基因可能参与了K5 6 2 /A0 2细胞的耐药机制 ,其中 7个基因在K5 6 2 /A0 2中被下调 ,5个基因被上调。本研究结果显示 ,NF H基因在K5 6 2 /A0 2细胞中高表达 ,并且 ,将NF H和mdr1反义核酸同时转入K5 6 2 /A0 2细胞后 ,可明显提高细胞内ADM浓度 ,而单独转入NF H反义核酸效果不明显。结论 K5 6 2 /A0 2细胞耐药表型的形成是多因素的 ,除了P 糖蛋白 (P gp)等常见因素外 ,可能还有NF Objective To study the molecular mechanism underlying multidrug resistance (MDR) and identify unknown genes that might be involved in drug resistance development in K562/A02 cells. Methods K562/A02 was induced by gradually increasing the ADM concentration in culture medium of K562 cells, the differential expression of associated genes between K562 and K562/A02 was determined with cDNA microarray. Overexpression of neurofilament protein NF H gene in K562/A02 cells was confirmed with RT PCR and immunocytochemistry. Anti sense oligodeoxynucleotides were transfected into K562/A02 cells by lipofectamine in order to further analyze the role of NF H in drug resistance. Results Comparing with the expression profiles, we found upregulation of 5 transcripts and downregulation of 7 transcripts in response to MDR of K562/A02 cells. The overexpression of NF H, one of the 5 upregulated genes, was confirmed. After being treated with antisense oligodeoxynucleotides of NF H and mdr1, the cellular adriamycin concentration increased significantly, but antisense NF H alone did not have significant effect on drug resistance phenotype. Conclusion The development of MDR in K562/A02 cells is multifactorial. NF H may be involved in the drug resistance of K562/A02, which may provide a new marker of diagnosis and a new target of therapy.
出处 《中华肿瘤杂志》 CAS CSCD 北大核心 2004年第6期328-332,共5页 Chinese Journal of Oncology
基金 国家自然科学基金资助项目 (3 0 2 715 15 ) 国家"九五"科技攻关资助项目 (96 90 6 0 1 2 3 )
关键词 NF-H基因 K562/A02细胞 多药耐药机制 MDR 阿霉素 K562/A02基因 Multidrug resistance cDNA microarray K562/A02 cells K562/A02 gene NF-H gene Gene expression
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  • 1Yang CZ, Luan FJ, Xiong DS, et al. Multidrug resistance in leukemia cell line K562/A02 induced by doxorubicin. Zhongguo Yao Li Xue Bao, 1995, 16: 333-337.
  • 2Davidoff MS, Middendorff R, Pusch W, et al. Sertoli and Leydig cells of the human testis express neuroilament triplet protein. Histochem Cell Biol, 1999, 111: 173-187.
  • 3Cucco C, Calabretta B. In vitro and in vivo reversal of multidrug resistance in a human leukemia-resistant cell line by mdr1 antisense oligodeoxynucleotides. Cancer Res, 1996, 56: 4332-4337.
  • 4Higgins CF. The multidrug resistance P-glycoprotein. Curr Opin Cell Biol, 1993, 5: 684-687.
  • 5Grant CE, Valdimarsson G, Hipfner DR, et al. Overexpression of multidrug resistance-associated protein(MRP) increases resistance to natural product drugs. Cancer Res, 1994, 54: 357-361.
  • 6Izquierdo MA, Scheffer GL, Flens MJ, et al. Major vault protein LRP-related multidrug resistance. Eur J Cancer, 1996, 32A: 979-984.
  • 7Doyle LA, Yang W, Abruzzo LY, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA, 1999, 96:2569.
  • 8Wessel I, Jensen PB, Falck J, et al. Loss of amino acids 1490Lys-Ser-Lys1492 in the COOH-terminal region of topoisomerase Ⅱalpha in human small cell lung cancer cells selected for resistance to etoposide results in an extranuclear enzyme localization. Ca
  • 9Volm M. Multidrug resistance and its reversal. Anticancer Res, 1998, 18: 2905-2917.
  • 10Hickman JA. Apoptosis and chemotherapy resistance. Eur J Cancer, 1996, 32A: 921-926.

同被引文献38

  • 1许杨,王益华,高纪东,叶珏,朱红霞,徐宁志,王兴宇,孙宗棠.干扰RNA对HepG2肝癌细胞内源性c-myc表达的抑制作用[J].中华肿瘤杂志,2004,26(8):458-460. 被引量:22
  • 2林秀梅,谢兆霞,秦群.甲基莲心碱、红霉素逆转K562/A02细胞多药耐药及其机制的研究[J].中华血液学杂志,2005,26(5):305-307. 被引量:19
  • 3Robey RW, Polgar O, Deeken J, et al. ABCG2: determining its relevance in clinical drug resistance [J]. Cancer Metastasis Rev, 2007, 26(1):39-57.
  • 4Appenzeller-Herzog C, Hauri HP. The ER-Golgi intermediate compartment (ERGIC): in search of its identity and function [J]. J Cell Sei, 2006,119( 11):2173-2183..
  • 5Haimeur A, Conseil G, Deeley RG, et al. The MRP-related and BCRP/ABCG2 muhidrug resistance proteins: biology, substrate specificity and regulation [J]. Curr Drug Metab, 2004, 5( 1 ):21-53.
  • 6Mao QC, Unadkat JD. Role of the breast cancer resistance protein (ABCG2) in drug transport[J]. AAPS ,2005,7 (1):El 19-133.
  • 7Wyles JP, Ridgway ND. VAMP-associated protein-A regulates partitioning of oxysterol-binding protein-related protein-9 between the endoplasmic reticulum and Golgi apparatus [J]. Exp Cell Res 2004,297 (2):533-547.
  • 8Lowery D M,Lim D,Yaffe M B.Structure and function of Polo-like kinases[J].Oncogene,2005,24(2):248-259.
  • 9Eckerdt F,Yuan J,Strebhardt K.Polo-like kinases and oncogenesis[J].Oncogene,2005,24(2):267-276.
  • 10Liu X,Erikson R L.Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells[J].Proc Natl Acad Sci USA,2003,100(10):5789-5794.

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