Introduction of a survivin gene-specific small inhibitory RNA inhibits growth of pancreatic cancer cells.
Introduction of a survivin gene-specific small inhibitory RNA inhibits growth of pancreatic cancer cells.
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发表时间：
2005-11
影响因子：
2
通讯作者：
N. Tsuji;K. Asanuma;D. Kobayashi;A. Yagihashi;N. Watanabe
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文献类型：
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作者：
N. Tsuji;K. Asanuma;D. Kobayashi;A. Yagihashi;N. Watanabe
背景：抗凋亡分子Survivin在各种来源的人类肿瘤中均有表达。由于该分子具有抑制细胞凋亡、促进细胞周期、促进Fas配体表达等多种功能，Survivin作为肿瘤治疗的靶点受到越来越多的关注。将Survivin特异性小分子抑制RNA(SiRNA)导入胰腺癌细胞，研究其对肿瘤细胞生长的影响。材料与方法分别用RT-PCR和Western blotting检测Survivin基因和蛋白的表达。用流式细胞仪进行DNA直方图分析。结果在PANC-1细胞中引入针对Survivin的siRNA后，Survivin基因和蛋白的表达分别下降了90%以上和未检测到的量，并导致细胞生长抑制。SiRNA转染体表现出明显的形态变化，包括细胞增大和多核。SiRNA转染体未出现细胞周期停滞，但发生了细胞凋亡。结论本研究结果表明，Survivin特异性siRNA作为一种新的肿瘤治疗方法值得进一步研究。
BACKGROUND The anti-apoptotic molecule survivin is expressed in human cancers of various origins. Since this molecule possesses multiple functions, including apoptosis inhibition, cell cycle promotion and enhancement of Fas ligand expression, survivin has attracted growing attention as a target in cancer treatment. A survivin-specific small inhibitory RNA (siRNA) was introduced into pancreatic cancer cells to investigate its effect on cancer cell growth. MATERIALS AND METHODS Survivin mRNA and protein expression were examined by RT-PCR and Western blotting, respectively. DNA histogram analysis was performed using a flow cytometer. RESULTS The introduction of survivin-specific siRNA reduced survivin mRNA and protein expression in PANC-1 cells by over 90% and to an undetected amount, respectively, and induced growth inhibition. The siRNA transfectants showed pronounced morphological changes including enlargement of cells and multinucleation. siRNA transfectants did not show cell cycle arrest, but underwent apoptosis. CONCLUSION Our data suggest that the use of survivin-specific siRNA deserves further investigation as a novel approach to cancer therapy.