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Updated: Jun 15, 2026

Development and Application of Rapamycin-regulated Tyrosine Phosphatases
06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

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

Ming-Ju Wu1, Chi-Hao Chang, Yung-Tsung Chiu

  • 1Division of Nephrology, Taichung Veterans General Hospital, Taichung, Taiwan. wmj530@gmail.com

Urologic Oncology
|March 9, 2010
PubMed
Abstract

Insights

Rapamycin effectively inhibits urothelial carcinoma development in rats by reducing tumor growth and cell migration. This mTORC1 inhibitor shows promise for preventing cancer in kidney transplant patients.

Area of Science:

  • Oncology
  • Transplantation Immunology
  • Pharmacology

Background:

  • Kidney transplant recipients have a high incidence of urothelial carcinoma.
  • Rapamycin, an mTOR Complex 1 inhibitor, is an alternative immunosuppressant with lower neoplastic potential.
  • The study investigates rapamycin's effects on urothelial carcinoma.

Purpose of the Study:

  • To evaluate the in vivo and in vitro effects of rapamycin on urothelial carcinoma.
  • To determine the anti-tumor mechanisms of rapamycin in urothelial carcinoma.

Main Methods:

  • A rat model of urothelial carcinoma was induced using N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN).
  • Rapamycin's anti-tumor effects were assessed via gross, microscopic, and Western blot analyses.
  • In vitro studies utilized T24 cells to evaluate rapamycin's mechanism of action.

Main Results:

  • Rapamycin significantly reduced tumor growth in the BBN-induced rat model (P < 0.001).
  • In vitro, rapamycin inhibited T24 cell proliferation, migration, and invasion, and decreased VEGF-A expression.
  • Rapamycin decreased phospho-mTOR, phospho-S6K, cyclin D1, and VEGF-A, while activating AKT in a rictor-dependent manner.

Conclusions:

  • Rapamycin demonstrates in vitro and in vivo potential to inhibit urothelial carcinoma development.
  • Rictor-dependent AKT activation is implicated as a downstream effect of mTORC1 inhibition by rapamycin.

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