Everolimus combined with cisplatin has a potential role in treatment of urothelial bladder cancer

Biomed Pharmacother. 2013 Mar;67(2):116-21. doi: 10.1016/j.biopha.2012.11.007. Epub 2012 Dec 26.

Abstract

Cisplatin (CDDP)-based chemotherapy is a commonly treatment for advanced urothelial carcinoma. However, episodes of cisplatin resistance have been referenced. Recently it has been reported that everolimus (RAD001) could have an important role to play in bladder-cancer treatment and that mTOR inhibitors may restore chemosensitivity in resistant tumours. The aim of this study was to assess RAD001 in vitro ability to enhance CDDP cytotoxicity in three human bladder-cancer cell lines. Over the course of 72h, the cells were exposed to different concentrations of CDDP and RAD001, isolated or combined. Treatment with CDDP statistically (P<0.05) decreased cell proliferation in cell lines in a dose-dependent manner. The anti-proliferative activity of CDDP used in combination with RAD001 was statistically significant (P<0.05) in the cell lines at all concentrations tested. RAD001 had a therapeutic effect when used in combination with CDDP and could therefore be a useful anti-cancer drug combination for patients with bladder cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Everolimus
  • Humans
  • In Situ Nick-End Labeling / methods
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives
  • Urinary Bladder Neoplasms / drug therapy*
  • Urothelium / pathology

Substances

  • Everolimus
  • Cisplatin
  • Sirolimus