RNA interference targeting Stat3 inhibits growth and induces apoptosis of human prostate cancer cells
RNA interference targeting Stat3 inhibits growth and induces apoptosis of human prostate cancer cells
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DOI：
10.1002/pros.20072
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发表时间：
2004-09-01
期刊：
影响因子：
2.8
通讯作者：
Gao, AC
中科院分区：
文献类型：
--
作者：
Lee, SO;Lou, W;Gao, AC
Stat 3是信号转导和转录激活（STAT）家族的成员，是介导细胞因子、肽生长因子和癌蛋白的信号传导的关键信号转导蛋白，并且在包括前列腺在内的许多癌症中被组成性激活。以往的研究表明，组成性激活的Stat 3通过促进细胞增殖和保护细胞凋亡在前列腺癌的发生和发展中起着重要作用。本研究旨在探讨RNA干扰技术阻断Stat 3表达和激活的可能性及其对人前列腺癌细胞生长的影响。我们确定了一个小的干扰RNA（siRNA）的特定的Stat 3和Stat 3的siRNA阻断Stat 3激活抑制人前列腺癌细胞的生长和Stat 3介导的基因表达，并诱导细胞凋亡。Stat 3 siRNA不抑制Stat 3失活的人前列腺癌细胞的增殖，也不诱导其凋亡。此外，Stat 3 siRNA抑制前列腺癌细胞中雄激素调节的前列腺特异性抗原（PSA）表达水平。这些结果表明，使用siRNA技术靶向Stat 3信号转导可作为治疗表达组成性激活的Stat 3的前列腺癌的新的治疗策略。(C)2004 Wiley-Liss，Inc.
Stat3, a member of the signal transduction and activation of transcription (STAT) family, is a key signal transduction protein that mediates signaling by cytokines, peptide growth factors, and oncoproteins and is constitutively activated in numerous cancers including prostate. Previous studies demonstrated that constitutively activated Stat3 plays an important role in the development and progression of prostate cancer by promoting cell proliferation and protecting against apoptosis. The present study was designed to investigate the potential use of RNA interference to block Stat3 expression and activation and the effect on the growth of human prostate cancer cells. We identified a small interfering RNA (siRNA) specific for Stat3 and demonstrate that blockade of Stat3 activation by the Stat3 siRNA suppresses the growth of human prostate cancer cells and Stat3-mediated gene expression and induces apoptotic cell death. The Stat3 siRNA does not inhibit the proliferation nor induces apoptosis of Stat3-inactive human prostate cancer cells. In addition, the Stat3 siRNA inhibits the levels of androgen-regulated prostate specific antigen (PSA) expression in prostate cancer cells. These results demonstrate that targeting Stat3 signaling using siRNA technique may serve as a novel therapeutic strategy for treatment of prostate cancer expressing constitutively activated Stat3. (C) 2004 Wiley-Liss, Inc.