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

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

研究成果: Article

22 引用 (Scopus)

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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 d-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 motilityrelated 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.

元の言語English
ページ(範囲)21628-21635
ページ数8
ジャーナルOncotarget
6
発行部数25
DOI
出版物ステータスPublished - 01-01-2015

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Oncology

これを引用

Inamoto, T., Taniguchi, K., Takahara, K., Iwatsuki, A., Takai, T., Komura, K., Yoshikawa, Y., Uchimoto, T., Saito, K., Tanda, N., Kouno, J., Minami, K., Uehara, H., Hirano, H., Nomi, H., Kiyama, S., Akao, Y., & Azuma, H. (2015). Intravesical administration of exogenous microRNA-145 as a therapy for mouse orthotopic human bladder cancer xenograft. Oncotarget, 6(25), 21628-21635. https://doi.org/10.18632/oncotarget.4129