Intravesical administration of exogenous microRNA-145 as a therapy for mouse orthotopic human bladder cancer xenograft
PDF | HTML | How to cite
Metrics: PDF 1933 views | HTML 2101 views | ?
Teruo Inamoto1, Kohei Taniguchi2, Kiyoshi Takahara1, Ayako Iwatsuki2, Tomoaki Takai1, Kazumasa Komura1, Yuki Yoshikawa1, Taizo Uchimoto1, Kenkichi Saito1, Naoki Tanda1, Junko Kouno1, Koichiro Minami1, Hirofumi Uehara1, Hajime Hirano1, Hayahito Nomi1, Satoshi Kiyama1, Yukihiro Akao2 and Haruhito Azuma1
1 Department of Urology, Osaka Medical College, Osaka, Japan
2 United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan
Teruo Inamoto, email:
Keywords: microRNA-145, intravesical instillation, bladder cancer
Received: March 06, 2015 Accepted: April 30, 2015 Published: May 12, 2015
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.