title: Intravesical administration of exogenous microRNA-145 as a therapy for mouse orthotopic human bladder cancer xenograft.
abstract: We previously reported that the level of microRNA (miR)-145 is attenuated in human bladder cancer cells. In this current study, we investigated whether intravesical administration of miR-145 could be a potential therapeutic strategy for controlling bladder cancer by using an orthotopic human bladder cancer xenograft model. Following transfection of 253J B-V cells with miR-145, the effects of the ectopic expression of miR-145 were examined by performing MTT, Western blotting analysis, Hoechst33342 staining, and wound healing assay in vitro. Also, a mouse orthotopic human bladder cancer model was established by inoculating 253J B-V cells into the bladder wall of mice. The anti-cancer effects of intravesical injections of miR-145 into these mice were then assessed. Transfection of 253J B-V cells with miR-145 induced apoptosis and suppression of cell migration in vitro. Western blotting showed that the levels of c-Myc, socs7, FSCN1, E-cadherin, β-catenin, and catenin δ-1 were decreased and that the PI3K/Akt and Erk1/2 signaling pathways were increased in compensatory fashion. In vivo, mice treated with miR-145 showed 76% inhibition of tumor growth, with a significant prolongation of animal survival (p = 0.0183 vs. control). Western blotting showed that both apoptosis and cell motility-related genes were significantly decreased as seen in vitro. Furthermore, PI3k/Akt and Erk1/2 signaling pathways, which were activated in a compensatory manner in vitro, were decreased in vivo. Intravesical administration of exogenous miR-145 was thus concluded to be a valid therapy for bladder cancer in this human bladder cancer xenograft model.
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Inamoto
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Taniguchi
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takahara
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Iwatsuki
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Takai
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Komura
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yoshikawa
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Taizo
authors.initials: T
authors.lastname: Uchimoto
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tanda
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Kouno
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Minami
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Uehara
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Hirano
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Hayahito
authors.initials: H
authors.lastname: Nomi
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kiyama
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akao
authors.affiliation: Department of Urology, Osaka Medical College, Osaka, Japan.
authors.forename: Haruhito
authors.initials: H
authors.lastname: Azuma
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000008:administration & dosage / Q000378:metabolism*; D009368:Neoplasm Transplantation; D015398:Signal Transduction; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: C541010:MIRN145 microRNA, human; D035683:MicroRNAs
keywords: bladder cancer; intravesical instillation; microRNA-145