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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, ?-catenin, and catenin ?-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.

SUBMITTER: Inamoto T

PROVIDER: S-EPMC4673291 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Intravesical administration of exogenous microRNA-145 as a therapy for mouse orthotopic human bladder cancer xenograft.

Inamoto Teruo T Taniguchi Kohei K Takahara Kiyoshi K Iwatsuki Ayako A Takai Tomoaki T Komura Kazumasa K Yoshikawa Yuki Y Uchimoto Taizo T Saito Kenkichi K Tanda Naoki N Kouno Junko J Minami Koichiro K Uehara Hirofumi H Hirano Hajime H Nomi Hayahito H Kiyama Satoshi S Akao Yukihiro Y Azuma Haruhito H

Oncotarget 20150801 25

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, Hoechst3334 ...[more]

PMID: 26036261

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Dataset Information

Intravesical administration of exogenous microRNA-145 as a therapy for mouse orthotopic human bladder cancer xenograft.

Publications

Intravesical administration of exogenous microRNA-145 as a therapy for mouse orthotopic human bladder cancer xenograft.

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