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XAF1抑制肝癌细胞增殖和诱导凋亡的实验研究 被引量：5

Experimental study on XAF1 for inhibiting tumorigenesis and inducing apoptosis in HCC Bel7404 nude mice xenografts
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摘要 目的X-染色体相关凋亡抑制蛋白(XIAP)相关因子1(XAF1)可与XIAP直接结合并拮抗其抗凋亡作用。本研究探讨XAF1基因在裸鼠体内抑制肝癌细胞增殖和诱导其凋亡的作用。方法应用免疫组织化学、TUNEL方法检测稳定高表达质粒DNA的肝癌细胞克隆Bel7404/XAF1、Bel7404/XAF1-AS和Bel7404/vector在体内的增殖和凋亡。结果Bel7404/XAF1组裸鼠肿瘤组织生长速度明显慢于其余两组的瘤组织(P<0.05),组成性高表达XAF1可以抑制裸鼠移植瘤的形成;TUNEL法检测Bel7404/vector的凋亡率为2.18%,Bel7404/XAF1凋亡率为7.09%,Bel7404/XAF1-AS凋亡率为2.91%(P<0.05)。结论XAF1能够在体内抑制肝癌细胞增殖和诱导其凋亡,XAF1有可能成为肝癌基因治疗的新靶点。 Objective To investigate the expression and the effects of XIAP associated factor 1 （XAF1） on tumorigenesis and apoptosis in the HCC Be[ 7404 nude mice xenografts. Methods Stable transfeetants Bel7404/XAF1, Bel- 7404/ XAF1-AS and Bel-7404/ Vector were constructed as we described before. Tumorigenesis was assessed by analyzing volume of the tumors in subcutaneous nude mice xenografts. Furthermore, we detected apoptosis of the nude mice xenografts through TUNEI. assay. Results In nude mice xenografts, Bel-7404/Vector and Bel-7404/ XAF1-AS formed localized tumors 10 days after subcutaneous injection , while visible tumor formed began at 28^th days after injection of Bel- 7404/XAF1 cells. The rates of tumor growth was significantly slower in Bel-7404/XAF1 transfectants than those in Bel7404/XAF1-AS and Bel 7404/vector transfeetants（P〈0.05） significantly. Through TUNEL assay,we found that the apoptosis rate of Bel7404/XAF1 was 7.09%, while the apoptosis rates were 2. 18% and 2.91% in Bel7404/vector and Bel7404/XAF1-AS respectively. Stable expression of XAF1 had significantly more spontaneous apoptosis in Bel7404/ XAF1 nude mice xenografts than that both in Bel7404/XAF1 The results showed that the overexpression of XAF1 in XAF1 may be a promising candidate for HCC gene therapy. AS and Bel-7404/vector（P〈0.05） significantly. Conclusion vivo induced apoptosis and inhibited Bel7404 cell growth.
作者 涂水平 史冬梅 马天乐 谭继宏 乔敏敏 章永平 江石湖
机构地区 上海交通大学附属瑞金医院消化科 上海复旦大学附属华东医院消化科
出处 《肝脏》 2008年第4期315-317,共3页 Chinese Hepatology
基金 国家自然科学基金(30100221和30572142)
关键词 X-染色体相关凋亡抑制蛋白 XAF1 肝细胞癌 细胞凋亡 X-chromosome linked inhibitor of apoptosis XAF1 Hepatocellular carcinoma Apoptosis
分类号 R735.7 [医药卫生—肿瘤] R730.3 [医药卫生—肿瘤]
  • 相关文献

参考文献14

  • 1Tu SP, Jiang XH,Lin MC, et al. Suppression of survivin expression inhibits in vivo tumorigenicity and angiogenesis in gastric cancer. Cancer Res, 2003, 63: 7724-7732.
  • 2Deveraux QL, Reed JC. lAP family proteins--suppressors of apoptosis. Genes Dev, 1999, 13: 239-252.
  • 3Holcik M, Gibson H, Korneluk RG. XIAP: apoptotic brake and promising therapeutic target. Apoptosis, 2001, 6: 253-251.
  • 4Liston P, Fong WG, Korneluk RG. The inhibitors of apoptosis: there is more to life than Bcl2. Oncogene, 2003, 22: 8568-8580.
  • 5Byun DS, Cho K, Ryu BK, et al. Hypermethylation of XIAP-associated factor 1, a putative tumor suppressor gene from the 17p13.2 locus, in human gastric adenoearcinomas. Cancer Res, 2003, 63 : 7068-7075.
  • 6Shiraki K, Sugimoto K, Yamanaka Y, et al. Overexpression of X- linked inhibitor of apoptosis in human hepatocellular carcinoma. Int J Mol Med,2003,12:705-708.
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  • 8史冬梅,马天乐,涂水平,谭继宏,乔敏敏,章永平,江石湖.X-染色体相关凋亡抑制蛋白相关因子1抑制肝癌细胞增殖和诱导凋亡的实验研究[J].中华消化杂志,2006,26(10):682-685. 被引量：13
  • 9Ma TL, Ni PH, Zhong J, et al. Low expression of XIAP-associated factor 1 in human eolorectal cancers. Chin J Dig Dis, 2005. 6: 10-14.
  • 10Ng KC, Campos El, Martinka M, et al. XAFI expression is significantly reduced in human melanoma. Invest Dermatol, 2004, 123: 1127-1134.

二级参考文献12

  • 1Tu SP,Jiang XH,Lin MC,et al.Suppression of survivin expression inhibits in vivo tumorigenicity and angiogenesis in gastric cancer.Cancer Res,2003,63:7724-7732.
  • 2Deveraux QL,Reed JC.IAP family proteins-suppressors of apoptosis.Genes Dev,1999,13:239-252.
  • 3Liston P,Fong WG,Korneluk RG.The inhibitors of apoptosis:there is more to life than Bcl2.Oncogene,2003,22:8568-8580.
  • 4Holcik M,Gibson H,Korneluk RG.XIAP:apoptotic brake and promising therapeutic target.Apoptosis,2001,6:253-261.
  • 5Byun DS,Cho K,Ryu BK,et al.Hypermethylation of XIAP-associated factor 1,a putative tumor suppressor gene from the 17p13.2 locus,in human gastric adenocarcinomas.Cancer Res,2003,63:7068-7075.
  • 6Shiraki K,Sugimoto K,Yamanaka Y,et al.Overexpression of X-linked inhibitor of apoptosis in human hepatocellular carcinoma.Int J Mol Med,2003,12:705-708.
  • 7Yamaguchi Y,Shiraki K,Fuke H,et al.Targeting of X-linked inhibitor of apoptosis protein or survivin by short interfering RNAs sensitize hepatoma cells to TNF-related apoptosis-inducing ligand-and chemotherapeutic agent-induced cell death.Oncol Rep,2005,14:1311-1316.
  • 8Ma TL,Ni PH,Zhong J,et al.Low expression of XIAP-associated factor 1 in human colorectal cancers.Chin J Dig Dis,2005,6:10-14.
  • 9Ng KC,Campos El,Martinka M,et al.XAF1 expression is significantly reduced in human melanoma.J Invest Dermatol,2004,123:1127-1134.
  • 10Xia Y,Novak R,Lewis J,et al.Xafl can cooperate with TNF alpha in the induction of apoptosis,independently of interaction with XIAP.Mol Cell Biochem,2006,286:67-76.

共引文献12

同被引文献37

  • 1HuiCen,ShuZheng,Yong-MingFang,Xiao-PingTang,QiDong.Induction of HSF1 expression is associated with sporadic colorectal cancer[J].World Journal of Gastroenterology,2004,10(21):3122-3126. 被引量：14
  • 2史冬梅,马天乐,涂水平,谭继宏,乔敏敏,章永平,江石湖.X-染色体相关凋亡抑制蛋白相关因子1抑制肝癌细胞增殖和诱导凋亡的实验研究[J].中华消化杂志,2006,26(10):682-685. 被引量：13
  • 3Liston P, Fong WG, Kelly NL, et al. Identification of XAF1 as an antagonist of XIAP anti-Caspase activity. Nat Cell Biol, 2001, 3 (2): 128-133.
  • 4Fong WG, Liston P, Rajcan-Separovic E, et al. Expression and genetic analysis of XIAP-associated factor 1 (XAF1) in cancer cell lines. Genomics, 2000, 70 (1): 113-122.
  • 5Ma TL, Ni PH, Zhong J, et al. Low expression of XIAP- associated factor 1 in human colorectal cancers. Chin J Dig Dis, 2005, 6 (1): 10-14.
  • 6Byun DS, Cho K, Ryu BK, et al. Hypermethylation of XIAP-associated factor 1, a putative tumor suppressor gene from the 17p13.2 locus, in human gastric adenocarcinomas. Cancer Res, 2003, 63 (21): 7068-7075.
  • 7Fang X, Liu Z, Fan Y, et al. Switch to full-length of XAF1 mRNA expression in prostate cancer cells by the DNA methylation inhibitor. Int J Cancer, 2006, 118 (10): 2485-2489.
  • 8Zou B, Chim CS, Zeng H, et al. Correlation between the single-site CpG methylation and expression silencing of the XAF1 gene in human gastric and colon cancers. Gastroenterology, 2006, 131 (6): 1835-1843.
  • 9Lee MG, Huh JS, Chung SK, et al. Promoter CpG hypermethylation and downregulation of XAF1 expression in human urogenital malignancies: implication for attenuated p53 response to apoptotic stresses. Oncogene, 2006, 25 (42): 5807-5822.
  • 10Lind GE, Thorstensen L, Lφvig T, et al. A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines. Mol Cancer, 2004, 3: 28.

引证文献5

二级引证文献11

肝脏
2008年 第4期

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