Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer
Masaki Nogawa, … , Yusaku Okada, Taira Maekawa
Masaki Nogawa, … , Yusaku Okada, Taira Maekawa
Published April 1, 2005
Citation Information: J Clin Invest. 2005;115(4):978-985. https://doi.org/10.1172/JCI23043.
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Article Oncology

Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer

Abstract

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 line, UM-UC-3LUC. 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 liposomes. We believe intravesical siRNA instillation against bladder cancer will be useful as a therapeutic tool.

Authors

Masaki Nogawa, Takeshi Yuasa, Shinya Kimura, Motoyoshi Tanaka, Junya Kuroda, Kiyoshi Sato, Asumi Yokota, Hidekazu Segawa, Yoshinobu Toda, Susumu Kageyama, Tatsuhiro Yoshiki, Yusaku Okada, Taira Maekawa

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Figure 1

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PLK-1 expression correlates with the progression of bladder cancer. (A) ...
PLK-1 expression correlates with the progression of bladder cancer. (A) PLK-1 staining in the tissue of bladder cancers. Strong immune reaction in high-grade bladder cancers (top and middle rows) and weak immune reaction in low-grade bladder cancers (bottom row) were typically observed by immunohistochemistry. Nuclear staining was performed with Mayer’s hematoxylin. The arrow indicates lymphatic invasion of cancer cells in the high-grade bladder cancer. Numbers indicate original magnifications. (B) Comparison of the survival curves between bladder cancers with high and those with low PLK-1 expression. (C) Western blotting analysis of PLK-1 expression in the tissues of bladder tumor (T) and normal bladder epithelium (N) of the same patients. (D) Western blotting analysis of PLK-1 expression in human bladder cancer and normal cells.