Prevention of the growth of bladder cancer by intravesical administration of small interfering RNA targeting PLK-1

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The mainstay in the management of invasive bladder cancer continues to be radical cystectomy. From the point of improvement of quality of life, however, therapies which preserve the bladder are desirable. We investigated the use of intravesical polo like kinase-1 (PLK-1) small interfering RNA (siRNA) against bladder cancer.Patients with bladder cancers expressing high levels of PLK-1 have a poor prognosis compared to 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 luciferase labeled bladder cancer cell line, 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 intravesical siRNA/cationic liposome inhibition of cancer growth in murine bladder. We believe intravesical siRNA instillation therapy against bladder cancer will be useful as a therapeutic tool.