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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)21628-21635
Number of pages8
JournalOncotarget
Volume6
Issue number25
DOIs
Publication statusPublished - 01-01-2015
Externally publishedYes

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Intravesical Administration
MicroRNAs
Heterografts
Urinary Bladder Neoplasms
Catenins
Western Blotting
Therapeutics
Transfection
Apoptosis
Cadherins
Phosphatidylinositol 3-Kinases
Wound Healing
Cell Movement
Neoplasms
Urinary Bladder
Staining and Labeling
In Vitro Techniques
Growth

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Inamoto, Teruo ; Taniguchi, Kohei ; Takahara, Kiyoshi ; Iwatsuki, Ayako ; Takai, Tomoaki ; Komura, Kazumasa ; Yoshikawa, Yuki ; Uchimoto, Taizo ; Saito, Kenkichi ; Tanda, Naoki ; Kouno, Junko ; Minami, Koichiro ; Uehara, Hirofumi ; Hirano, Hajime ; Nomi, Hayahito ; Kiyama, Satoshi ; Akao, Yukihiro ; Azuma, Haruhito. / Intravesical administration of exogenous microRNA-145 as a therapy for mouse orthotopic human bladder cancer xenograft. In: Oncotarget. 2015 ; Vol. 6, No. 25. pp. 21628-21635.
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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 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.",
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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, vol. 6, no. 25, pp. 21628-21635. https://doi.org/10.18632/oncotarget.4129

Intravesical administration of exogenous microRNA-145 as a therapy for mouse orthotopic human bladder cancer xenograft. / Inamoto, Teruo; Taniguchi, Kohei; Takahara, Kiyoshi; Iwatsuki, Ayako; Takai, Tomoaki; Komura, Kazumasa; Yoshikawa, Yuki; Uchimoto, Taizo; Saito, Kenkichi; Tanda, Naoki; Kouno, Junko; Minami, Koichiro; Uehara, Hirofumi; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi; Akao, Yukihiro; Azuma, Haruhito.

In: Oncotarget, Vol. 6, No. 25, 01.01.2015, p. 21628-21635.

Research output: Contribution to journalArticle

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T1 - Intravesical administration of exogenous microRNA-145 as a therapy for mouse orthotopic human bladder cancer xenograft

AU - Inamoto, Teruo

AU - Taniguchi, Kohei

AU - Takahara, Kiyoshi

AU - Iwatsuki, Ayako

AU - Takai, Tomoaki

AU - Komura, Kazumasa

AU - Yoshikawa, Yuki

AU - Uchimoto, Taizo

AU - Saito, Kenkichi

AU - Tanda, Naoki

AU - Kouno, Junko

AU - Minami, Koichiro

AU - Uehara, Hirofumi

AU - Hirano, Hajime

AU - Nomi, Hayahito

AU - Kiyama, Satoshi

AU - Akao, Yukihiro

AU - Azuma, Haruhito

PY - 2015/1/1

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N2 - 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.

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