期刊文献+

Effect of small interfering RNA targeting survivin gene on biological behaviour of bladder cancer 被引量:13

Effect of small interfering RNA targeting survivin gene on biological behaviour of bladder cancer
原文传递
导出
摘要 Background Bladder cancer is the most common type of urinary system tumours. It is frequently associated with genetic mutations that deregulate the cell cycle and render these tumours resistant to apoptosis. Survivin, a newly discovered member inhibitor of apoptosis protein (IAP) family in several human cancers, by inducing cell proliferation and inhibiting apoptosis is frequently activated in bladder cancer. We studied the influence of small interfering RNA (siRNA) targeting survivin on the biological behaviour of bladder cancer cells. Methods A double strand survivin target sequence specific siRNA was designed and synthesized. After transfection of bladder cancer cell line T24 by siRNA/liposome complex with increasing concentrations (50-200 nmol/L), the transfectant cells were intratumourally injected at different doses (5 μg or 50 μg). The effects were measured in vitro and in vivo.Results The selected siRNA efficiently down-regulated survivin mRNA expression in a dose and time dependent manner. The maximal effect was achieved at the concentration of 100 nmol/L, at which survivin expression level was down-regulated by 75.91%. The inhibition rate of cell growth was 55.29% (P〈0.01) and the markedly increased apoptotic rate was 45.70% (P〈0.01). In vivo intratumoural injection of 50 μg siRNA-survivin could notably orevent the growth of bladder cancer (P〈0.01) in xenografted animals.Conclusion The application of siRNA-survivin could markedly inhibit survivin expression in bladder cancer cell line by inducing apoptosis and inhibiting the growth of the tumour. It may become a new gene therapy tool for bladder cancer. Background Bladder cancer is the most common type of urinary system tumours. It is frequently associated with genetic mutations that deregulate the cell cycle and render these tumours resistant to apoptosis. Survivin, a newly discovered member inhibitor of apoptosis protein (IAP) family in several human cancers, by inducing cell proliferation and inhibiting apoptosis is frequently activated in bladder cancer. We studied the influence of small interfering RNA (siRNA) targeting survivin on the biological behaviour of bladder cancer cells. Methods A double strand survivin target sequence specific siRNA was designed and synthesized. After transfection of bladder cancer cell line T24 by siRNA/liposome complex with increasing concentrations (50-200 nmol/L), the transfectant cells were intratumourally injected at different doses (5 μg or 50 μg). The effects were measured in vitro and in vivo.Results The selected siRNA efficiently down-regulated survivin mRNA expression in a dose and time dependent manner. The maximal effect was achieved at the concentration of 100 nmol/L, at which survivin expression level was down-regulated by 75.91%. The inhibition rate of cell growth was 55.29% (P〈0.01) and the markedly increased apoptotic rate was 45.70% (P〈0.01). In vivo intratumoural injection of 50 μg siRNA-survivin could notably orevent the growth of bladder cancer (P〈0.01) in xenografted animals.Conclusion The application of siRNA-survivin could markedly inhibit survivin expression in bladder cancer cell line by inducing apoptosis and inhibiting the growth of the tumour. It may become a new gene therapy tool for bladder cancer.
出处 《Chinese Medical Journal》 SCIE CAS CSCD 2006年第20期1734-1739,共6页 中华医学杂志(英文版)
基金 This work was supported by the grants from the Talent Man Foundation of Jiansu Province (No. RC2003094) as well as the Science Foundation of Jiansu Province (No. H200517).
关键词 SURVIVIN RNA interference bladder neoplasms survivin RNA interference bladder neoplasms
  • 相关文献

参考文献10

  • 1Sharp JD,,Hausladen DA,Maher MG,Wheeler MA,Altieri DC,Weiss RM.Bladder cancer detection with urinary survivin, an inhibitor of apoptosis[].Frontiers in Bioscience.2002
  • 2Uchida H,,Tanaka T,Sasaki K,Kato K,Dehari H,Ito Y, et al.Adenovirus-mediated transfer of siRNA against survivin induced apoptosis and attenuated tumor cell growth in vitro and in vivo[].Molecular Therapy.2004
  • 3Kappler M,,Bache M,Bartel F,Kotzsch M,Panian M,Wurl P, et al.Knock-down of survivin expression by small interfering RNA reduces the clonogenic survival of human sarcoma cell lines independently of p53[].Cancer Gene Therapy.2004
  • 4Salz W,,Eisenberg D,Plescia J,Garlick DS,Weiss RM,Wu XR, et al.A survivin gene signature predicts aggressive tumor behavior[].Cancer Research.2005
  • 5Rodriguez JA,,Span SW,Ferreira CGM,Kruyt FAE,Giaccone G.CRM1-mediated nuclear export determines the cytoplasmic localization of the antiapoptotic protein survivin[].Experimental Cell Research.2002
  • 6Williams NS,,Gaynor RB,Scoggin S,Verma U,Gokaslan T,Simmang C, et al.Identification and validation of genes involved in the pathogenesis of colorectal cancer using cDNA microarrays and RNA interference[].Clinical Cancer Research.2003
  • 7Li FZ,,Ambrosini G,Chu EY,Plescia J,Tognin S,Marchisio PC, et al.Control of apoptosis and mitotic spindle check point by survivin[].Nature.1998
  • 8Shin S,,Sung BJ,Cho YS,Kim HJ,Ha NC,Hwang JI, et al.An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7[].Biochemistry.2001
  • 9Mello CC,,Conte D Jr.Revealing the world of RNA interference[].Nature.2004
  • 10Masaki N,,Takashi YS,Shinya KR,Motoyoshi TK,Junya KD,Kivoshi ST, et al.Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer[].The Journal of Clinical Investigation.2005

同被引文献27

引证文献13

二级引证文献31

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