Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer
Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer
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DOI：
10.1172/jci200523043
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发表时间：
2005-04-01
影响因子：
15.9
通讯作者：
Maekawa, T
中科院分区：
文献类型：
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作者：
Nogawa, M;Yuasa, T;Maekawa, T
浸润性膀胱癌治疗的主要方法仍然是根治性膀胱切除术。然而，关于生活质量的改善，需要保留膀胱的疗法。我们研究了膀胱内PLK-1小干扰RNA（siRNA）对膀胱癌的作用。与低表达的患者相比，PLK-1高表达的膀胱癌患者预后较差。siRNA/阳离子脂质体可抑制膀胱癌细胞内源性PLK-1的表达，并呈时间和剂量依赖性。结果，PLK-1功能被破坏。观察到双极纺锤体形成的抑制、细胞周期蛋白B1的积累、细胞增殖的减少和细胞凋亡的诱导。为了确定siRNA/脂质体在体内的功效，我们使用LUC标记的膀胱癌细胞细颗粒UM-UC-3（Luc）建立了原位小鼠模型。PLK-1 siRNA成功转染到细胞中，降低了PLK-1的表达，并阻止了该小鼠模型中膀胱癌的生长。据我们所知，这是通过膀胱内siRNA/阳离子脂质体抑制小鼠膀胱中癌症生长的第一个证明。我们相信膀胱内siRNA灌注治疗膀胱癌将是一种有用的治疗工具。
The mainstay in the management of invasive bladder cancer continues to be radical cystectomy. With regard to improvement of quality of life, however, therapies that preserve the bladder are desirable. We investigated the use of intravesical PLK-1 small interfering RNA (siRNA) against bladder cancer. Patients with bladder cancers expressing high levels of PLK-1 have a poor prognosis compared with patients with low expression. Using siRNA/cationic liposomes, the expression of endogenous PLK-1 could be suppressed in bladder cancer cells in a time-and dose-dependent manner. As a consequence, PLK-1 functions were disrupted. Inhibition of bipolar spindle formation, accumulation of cyclin B1, reduced cell proliferation, and induction of apoptosis were observed. In order to determine the efficacy of the siRNA/liposomes in vivo, we established an orthotopic mouse model using a LUC-labeled bladder cancer cell fine, UM-UC-3(Luc). PLK-1 siRNA was successfully transfected into the cells, reduced PLK-1 expression, and prevented the growth of bladder cancer in this mouse model. This is the first demonstration, to our knowledge, of inhibition of cancer growth in the murine bladder by intravesical siRNA/cationic hposomes. We believe intravesical siRNA instillation against bladder cancer will be useful as a therapeutic tool.