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

被引：28

作者：

Inamoto, Teruo ^{[1
]}

Taniguchi, Kohei ^{[2
]}

Takahara, Kiyoshi ^{[1
]}

Iwatsuki, Ayako ^{[2
]}

Takai, Tomoaki ^{[1
]}

Komura, Kazumasa ^{[1
]}

Yoshikawa, Yuki ^{[1
]}

Uchimoto, Taizo ^{[1
]}

Saito, Kenkichi ^{[1
]}

Tanda, Naoki ^{[1
]}

Kouno, Junko ^{[1
]}

Minami, Koichiro ^{[1
]}

Uehara, Hirofumi ^{[1
]}

Hirano, Hajime ^{[1
]}

Nomi, Hayahito ^{[1
]}

Kiyama, Satoshi ^{[1
]}

Akao, Yukihiro ^{[2
]}

Azuma, Haruhito ^{[1
]}

机构：

[1] Osaka Med Coll, Dept Urol, Osaka, Japan

[2] Gifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, Gifu, Japan

来源：

ONCOTARGET | 2015年 / 6卷 / 25期

关键词：

microRNA-145; intravesical instillation; bladder cancer; COLON-CANCER; HIGH-RISK; COLORECTAL TUMORS; DOWN-REGULATION; CELLS; AND-145; EXPRESSION; CLUSTER; TARGET; GROWTH;

D O I：

10.18632/oncotarget.4129

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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, beta-catenin, and catenin delta-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.

引用

页码：21628 / 21635

页数：8

共 22 条

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