期刊文献+

缺氧对人小细胞肺癌H446细胞基因组DNA甲基化水平的影响 被引量:1

Hypoxia induces DNA methylation imbalance in human small cell lung cancer cells H446
原文传递
导出
摘要 目的研究缺氧对人小细胞肺癌H446细胞基因组DNA甲基化水平的影响。方法体外培养人小细胞肺癌细胞H446,置于缺氧(3%O2)条件下培养,分别于0、12、24、48、72 h后提取细胞基因组DNA,用甲基化敏感性随机引物PCR(MS-AP-PCR)方法检测基因组DNA甲基化状态。结果在缺氧状态下,H446细胞经酶解后的扩增谱带明显增多,且荧光强度较强,以24 h后明显,表明H446细胞基因组DNA甲基化水平在缺氧24 h后即发生明显升高,主要表现为多位点的异常甲基化。结论缺氧可能是造成肿瘤细胞内甲基化失衡的重要原因之一。 Objective To investigate the influence of hypoxia on the methylation level of genomic DNA in human small cell lung cancer H446 cells.Methods H446 cells were cultured under the hypoxic condition(3%O2) for different time periods(0,12,24,48 and 72 h respectively).Those cultured under normal condition served as control.The genomic DNA methylation level was detected by methylation sensitivity random primers PCR(MA-AS-PCR) after DNA extraction.Results Compared with the normoxic control group,the quantity and fluorescence intensity of amplified products of hypoxic experimental group were much higher,especially after 24 h.This indicated that the genomic DNA methylation level in the H446 cells was significantly changed when were treated by hypoxia,and represented mainly as multifocal abnormal methylation.Conclusion Hypoxia might be one of the key causer inducing unbalanced methylation in cancer cells.
出处 《第三军医大学学报》 CAS CSCD 北大核心 2011年第20期2145-2147,共3页 Journal of Third Military Medical University
基金 成都军区医学科研计划课题(MB09010)~~
关键词 缺氧 小细胞 DNA甲基化 细胞系 肿瘤 hypoxia carcinoma small cell DNA methylation cell line tumor
  • 相关文献

参考文献9

  • 1Shaw R J, Omar M M, Rokadiya S, et al. Cytoglobin is upregulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer[J]. Br J Cancer, 2009, 101 ( 1 ) : 139 - 144.
  • 2郭芮伶,吴国明,戢福云.缺氧对人小细胞肺癌H446细胞DNA错配修复基因MLH1、MSH2表达的影响及其机制探讨[J].中国癌症杂志,2008,18(1):26-29. 被引量:4
  • 3Skowronski K, Dubey S, Rodenhiser D, et al. Ischemia dysregulates DNA methyltransferases and p16(INK4a) methylation in human colorectal cancer cells[ J]. Epigenetics, 2010, 5 (6) : 547 - 556.
  • 4Zhou X, Sun H, Chen H, et al. Hypoxia induces trimethylated H3 lysine 4 by inhibition of JARID1A demethylase[J]. Cancer Res, 2010, 70(10) : 4214 -4221.
  • 5Watson J A, Watson C J, McCann A, et al. Epigenetics, the epicenter of the hypoxic response [ J ]. Epigenetics, 2010, 5 (4) : 293 - 296.
  • 6Yang J, Ledaki I, Turley H, et al. Role of hypoxia-inducible factors in epigenetic regulation via histone demethylases [ J ]. Ann N Y Acad Sci, 2009, 1177:185-197.
  • 7Whiteside M A, Piyathilake C J, Bushel1 T M, et al. Intrinsic cisplatin resistance in lung and ovarian cancer ceils propagating in medium acutely depleted of folate[J]. Nutr Cancer., 2006, 54(2) : 274 -284.
  • 8郭芮伶,吴国明,李海东,潘峰,李文碧,戢福云,钱桂生.人小细胞肺癌多药耐药细胞H446/CDDP基因组DNA甲基化状态的变化[J].第三军医大学学报,2010,32(23):2533-2535. 被引量:4
  • 9Shahrzad S, Bertrand K, Minhas K, et al. Induction of DNA hypomethylation by tumor hypoxia[J]. Epigenetics, 2007, 2(2) : 119 -125.

二级参考文献21

  • 1钱频,戢福云,钱桂生,黄桂君,陈琰,郭芮琳.顺铂诱导人小细胞肺癌多药耐药细胞系NCI-H446/CDDP的建立及其生物学特征分析[J].解放军医学杂志,2004,29(12):1052-1054. 被引量:11
  • 2Brown R, Glasspool R. Epigenetic modulation of resistance to chemotherapy? [J]. Ann Oncol, 2007, 18(9) : 1429-1430.
  • 3Di-Nicolantonio F, Mercer S J, Knight L A, et al. Cancer cell adaptation to chemotherapy[J]. BMC Cancer, 2005, 5: 78.
  • 4Glasspool R M, Teodoridis J M, Brown R. Epigenetics as a mechanism driving polygenic clinical drug resistance [ J ]. Br J Cancer, 2006, 94 (8) : 1087 -1092.
  • 5Tian K, Jurukovski V, Wang X P, et al. Epigenetic regulation of WTH3 in primary and cultured drug-resistant breast cancer cells [ J ]. Cancer Res, 2005, 65(21 ) :10024 - 10031.
  • 6Ibanez-de-Caceres I, Cortes-Sempere M, Moratilla C, et al. IGFBP-3 hy- permethylation-derived deficiency mediates cisplatin resistance in nonsmall-cell lung cancer[ J]. Oncogene, 2010, 29( 11 ) : 1681 - 1690.
  • 7Chang X, Monitto C L, Demokan S, et al. Identification of hypermethylated genes associated with cisplatin resistance in human cancers [ J ]. Cancer Res, 2010, 70(7): 2870-2879.
  • 8Chavez-Blanco A, Perez-Plasencia C, Perez-Cardenas E, et al. Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines [ J ].Cancer Cell Int, 2006, 6: 2.
  • 9Bram E E, Stark M, Raz S, et al. Chemotherapeutic drug-induced ABCG2 promoter demethylation as a novel mechanism of acquired multidrug resistance[ J ]. Neoplasia, 2009, 11 (12) : 1359 - 1370.
  • 10Sonnemann J, Kumar K S, Heesch S, et al. Histone deacetylase in- hibitors induce cell death and enhance the susceptibility to ionizing radiation, etoposide, and TRAIL in mednlloblastoma cells[ J]. Int J Oncol, 2006, 28 ( 3 ) : 755 - 766.

共引文献6

同被引文献24

  • 1张丽霞,潘世扬,陈丹,谢而付,高丽,束永前,陆祖宏,程璐,杨迪,张寄南.肺癌细胞株APC基因启动子甲基化对其转录的影响[J].癌症,2007,26(6):576-580. 被引量:10
  • 2JACKMAN D M,JOHNSON B E. Small - cell lung cancer[ J].Lancet, 2005, 366(9494) : 1385 -1396.
  • 3D'ANGELO S P, PIETANZA M C. The molecular pathogenesis ofsmall cell lung cancer[ J]. Cancer Biol Ther, 2010, 10(1) : 1 -10.
  • 4EGGER G,LIANG G, APARICIO A,et al. Epigenetics in hu-man disease and prospects for epigenetic therapy [ J ]. Nature,2004, 429(6990) ; 457 -463.
  • 5FEINBERG A P,TYCKO B. The history of cancer epigenetics[J]. Nat Rev Cancer, 2004,4(2) : 143 -153.
  • 6LAIRD P W. The power and the promise of DNA methylationmarkers[J]. Nat Rev Cancer, 2003,3(4) : 253 -266.
  • 7GRANDORI C, EISENMAN R N. Myc target genes[ J]. TrendsBiochem Sci, 1997, 22(5) : 177-181.
  • 8KRYSTAL G,BIRRER M,WAY J, et al. Multiple mechanismsfor transcriptional regulation of the myc gene family in small - celllung cancer[J]. Mol Cell Biol, 1988 , 8(8) : 3373 -3381.
  • 9LIN R K, HSUB H S, CHANG J W, et al. Alteration of DNAmethyltransferases contributes to 5'CpG methylation and poor prog-nosis in lung cancer [ J ]. Lung Cancer, 2007 , 55 ( 2 ) : 205 -213.
  • 10HARRIS C C. p53 tumor suppressor gene: from the basic researchlaboratory to the clinic-an abridged historical perspective[ J].Carcinogenesis, 1996, 17(6) : 1187 -1198.

引证文献1

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部