Gene interactions and pathways from curated databases and text-mining
Urol Oncol 2012, PMID: 20207175

Rictor-dependent AKT activation and inhibition of urothelial carcinoma by rapamycin.

Wu, Ming-Ju; Chang, Chi-Hao; Chiu, Yung-Tsung; Wen, Mei-Chin; Shu, Kuo-Hsiung; Li, Jian-Ri; Chiu, Kun-Yuan; Chen, Yen-Ta


We previously reported a very high cumulative incidence of urothelial carcinoma in Taiwanese kidney transplant recipients. Rapamycin, the inhibitor of mTOR Complex 1, provides alternative immunosuppressive therapy after kidney transplantation with less neoplastic potential. We examined the in vivo and in vitro effects of rapamycin on urothelial carcinoma.


The rat model of urothelial carcinoma was induced by 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in Fischer F344 rats. The anti-tumor effect of rapamycin was assessed grossly, microscopically, and by Western blot analysis. The mechanism of rapamycin's attenuation of urothelial carcinoma was also evaluated by T24 cells.


Rapamycin significantly reduced urinary bladder tumor growth in the rat model of 0.05% BBN-induced urothelial carcinoma (P < 0.001). The blood trough levels of rapamycin were correlated with the occurrence of urothelial carcinoma. In vitro, rapamycin also inhibited the cell proliferation, migration, and invasion, as well as the protein expression of vascular endothelial growth factor-A of T24 urothelial carcinoma cells, whereas rapamycin did not induce significant apoptosis in T24 cells. Rapamycin decreased the expression of phospho-mTOR, phospho-S6K, cyclin D1, and VEGF-A. Rapamycin also activated AKT in T24 cells in the rat model of urothelial carcinoma. The rapamycin-associated activation of AKT was inhibited by rictor siRNA, but not raptor siRNA.


This study provides in vitro and in vivo evidence that rapamycin may inhibit the development of urothelial carcinoma. The present findings also suggest rictor-dependent AKT activation as a consequence of mTORC1 inhibition.

Diseases/Pathways annotated by Medline MESH: Carcinoma, Transitional Cell, Disease Models, Animal, Urinary Bladder Neoplasms
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Text Mining Data

AKT → Rictor: " Rictor dependent AKT activation and inhibition of urothelial carcinoma by rapamycin "

AKT ⊣ mTORC1: " The present findings also suggest rictor dependent AKT activation as a consequence of mTORC1 inhibition "

Manually curated Databases

No curated data.