Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer.
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-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 liposomes. We believe intravesical siRNA instillation against bladder cancer will be useful as a therapeutic tool.
Nogawa
Masaki
M
Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan.
Yuasa
Takeshi
T
Kimura
Shinya
S
Tanaka
Motoyoshi
M
Kuroda
Junya
J
Sato
Kiyoshi
K
Yokota
Asumi
A
Segawa
Hidekazu
H
Toda
Yoshinobu
Y
Kageyama
Susumu
S
Yoshiki
Tatsuhiro
T
Okada
Yusaku
Y
Maekawa
Taira
T
D000283:Administration, Intravesical; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D015653:Cystectomy; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008081:Liposomes / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D001743:Urinary Bladder / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000097869:Polo-Like Kinase 1
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D008081:Liposomes; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1