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肝癌细胞对5-氮杂-2′-脱氧胞苷的敏感性与细胞总DNA甲基化水平无关

No correlation between the sensitivity to 5-aza-dC and the global DNA methylation level in hepatocelullar carcinoma cells
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摘要 目的比较不同肝癌细胞株对5-氮杂-2′-脱氧胞苷(5-aza-dC)的敏感性,探讨肝癌细胞对5-aza—dC的敏感性是否与细胞总DNA甲基化水平有关。方法用不同剂量(0.5、5.0、10.0μmol/L)的5-aza—dC处理肝癌细胞株(HepG2、QGY7701和HepG2.2.15细胞)及正常肝细胞株L02,比较不同浓度处理前后的细胞增殖抑制率,比较10μmol/L 5-aza-dC处理前后的Caspase-3活性及细胞DNA片段化水平(5-溴脱氧尿嘧啶核苷掺入率),比较不同细胞总DNA甲基化水平。组间检测结果比较采用t检验。结果5-aza—dC对HepG2、QGY7701、HepG2.2.15、L02细胞的半数抑制浓度分别为0.5、0.5、4.5、11.4μmol/L,与HepG2细胞和QGY7701细胞相比,HepG2.2.15细胞和L02细胞对5aza—dC不敏感。HepG2和QGY7701细胞中Caspase-3的活性升高较L02和HepG2.2.15细胞明显(P值均〈0.05),QGY7701细胞中5-溴脱氧尿嘧啶核苷掺入率升高较L02细胞明显(P〈0.05)。L02、HepG2、QGY7701和HepG2.2.15细胞的DNA总甲基化水平分别为11.7%±0.9%、10.9%±1.3%、11.7%±1.7%和12.2%±1.0%,差异无统计学意义(P值均〉0.05)。结论细胞对5-aza-dC的敏感性与细胞总DNA甲基化水平无关。 Objective To compare the sensitivity of different hepatocelullar carcinoma (HCC) cell lines (HepG2, QGY7701, HepG2.2.15) and the normal liver cell line L02 to 5-aza-dC, an DNA methyltransferase inhibitor, and to explore the relationship between global DNA methylation level and the sensitivity to 5-aza- dC. Methods HepG2, QGY7701, HepG2.2.15 and L02 cells were treated with 5-aza-dC at different concentration, cell proliferation was measured by MTT method, cell apoptosis was detected by measuring caspase 3 activity and cellular DNA fragmentation ELISA. Results Compared to HepG2 and QGY7701 cells, HepG2.2.15 were less sensitive to the treatment of 5-aza-dC; the normal liver cell line L02 was less sensitive to 5-aza-dC than the HCC cell lines. Conclusions The sensitivity to 5-aza-dC of HCC cell lines and normal liver cells is not correlated with the global DNA methylation level.
出处 《中华肝脏病杂志》 CAS CSCD 北大核心 2010年第4期284-287,共4页 Chinese Journal of Hepatology
基金 重庆市自然科学基金(2007BB5308)
关键词 肝细胞 脱氧胞苷 DNA甲基化 CASPASE类 Carcinoma, hepatocellular Deoxycytidine DNA methylation Caspase
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参考文献10

  • 1Herath NI,Leggett BA,MacDonald GA.Review of genetic and epigenetic alterations in hepatocarcinogenesis.J Gastroenterol Hepatol,2006,21:15-21.
  • 2Christman JK.5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation:mechanistic studies and their implications for cancer therapy.Oncogene,2002,21:5483-5495.
  • 3Niwa Y,Kanda H,Shikauchi Y,et al.Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma.Oncogene,2005,24:6406-6417.
  • 4Yau TO,Chan CY,Chan KL,et al.HDPR1,a novel inhibitor of the WNT/beta-catenin signaling,is frequently downregulated in hepatocellular carcinoma:involvement of methylation-mediated gene silencing.Oncogene,2005,24:1607-1614.
  • 5Kubo T,Yamamoto J,Shikanchi Y,et al.Apoptotic speck proteinlike,a highly homologous protein to apoptotic speck protein in the pyrin domain,is silenced by DNA methylation and induces apoptosis in human hepatocellular carcinoma.Cancer Res,2004,64:5 172-5177.
  • 6Fukai K,Yokosuka O,Chiba T,et al.Hepatocyte growth factor activator inhibitor 2/placental bikunin(HAI-2/PB)gene is frequently hypermethylated in human hepatocellular carcinoma.Cancer Res,2003,63:8674-8679.
  • 7Wang XM,Wang X,Li J,et al.Effects of 5-azacytidine and butyrate on differentiation and apoptosis of hepatic cancer cell lines.Ann Surg,1998,227:922-931.
  • 8Kanda T,Tada M,Imazeki F,et al.5-aza-2'-deoxycytidine sensitizes hepatoma and pancreatic cancer cell lines.Oncol Rep,2005,14:975-979.
  • 9谢静,王锋,梅浙川,唐开福,任红.TSA对不同肝癌细胞株增殖和凋亡的作用及其对HBV复制的影响[J].重庆医科大学学报,2008,33(9):1025-1028. 被引量:7
  • 10Sells MA,Chen ML,Acs G.Production of hepatitis B virus particles in Hep G2 cells transfected with cloned hepatitis B virus DNA.Proc Natl Acad Sci U S A.1987,84:1005-1009.

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