Blocking IKKα expression inhibits prostate cancer invasiveness.
Blocking IKKα expression inhibits prostate cancer invasiveness.
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DOI：
10.1007/s11095-010-0351-z
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发表时间：
2011-06
影响因子：
3.7
通讯作者：
Cheng K
中科院分区：
文献类型：
--
作者：
Mahato R;Qin B;Cheng K
IKKα是前列腺癌炎症和转移的关键介质。在本研究中，我们打算使用合成的siRNA沉默IKKα在前列腺癌细胞中的表达，并检查它们对肿瘤细胞侵袭和生长的生物学效应。设计了三种针对IKKα mRNA不同区域的合成siRNA，并在PC-3和DU 145细胞中测定了沉默效果。通过创伤愈合实验、迁移实验、侵袭实验、细胞贴壁实验、细胞增殖实验和细胞周期分析，研究了IKKα siRNA对前列腺癌细胞的生物学效应。我们已经鉴定出有效的siRNA，可以沉默IKKα高达74%。抑制IKKα可降低前列腺癌细胞的伤口愈合、迁移、侵袭和细胞粘附能力。在存在RANKL的情况下也观察到类似的抗侵袭作用。而沉默IKKα基因对细胞增殖和细胞周期分布的影响可忽略不计。这项研究提供了令人信服的证据表明，IKKα在前列腺癌的侵袭和转移中起主要作用，但在细胞增殖中不起作用。因此，用siRNA沉默IKKα可能为前列腺癌患者提供一种有希望的治疗策略。
IKKα has been recently identified as a key mediator of the inflammation and metastasis in prostate cancer. In the present study, we intend to silence the IKKα expression in prostate cancer cells using synthetic siRNAs and examine their biological effects on tumor cell invasiveness and growth. Three synthetic siRNAs targeting different regions of the IKKα mRNA were designed, and the silencing effect was determined in PC-3 and DU145 cells. Numerous studies, including wound-healing assay, migration assay, invasion assay, cell attachment assay, cell proliferation, and cell cycle analysis, were conducted to investigate the biological effects of the IKKα siRNAs on prostate cancer cells. We have identified potent siRNAs that can silence the IKKα up to 74%. Inhibition of IKKα reduced the wound healing, migration, invasion and cell attachment capabilities of prostate cancer cells. Similar anti-invasive effects were also observed in the presence of RANKL. However, silencing of IKKα only showed a negligible effect on cell proliferation and cell cycle distribution. This study presents compelling evidence that IKKα plays a major role in prostate cancer invasion and metastasis, but not in cell proliferation. Silencing of IKKα with siRNA may therefore provide a promising therapeutic strategy for prostate cancer patients.