title: Everolimus combined with cisplatin has a potential role in treatment of urothelial bladder cancer.
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.
authors: Genetic Service, Cytogenetic Laboratory, Hospital Center of Trás-os-Montes and Alto Douro, 5000-508, Vila Real, Portugal. mlleite@chtmad.min-saude.pt
authors: Rosário
authors: R
authors: Pinto-Leite
authors: Regina
authors: R
authors: Arantes-Rodrigues
authors: Carlos
authors: C
authors: Palmeira
authors: Bruno
authors: B
authors: Colaço
authors: Carlos
authors: C
authors: Lopes
authors: Aura
authors: A
authors: Colaço
authors: Céu
authors: C
authors: Costa
authors: Vítor Moreira
authors: VM
authors: da Silva
authors: Paula
authors: P
authors: Oliveira
authors: Lúcio
authors: L
authors: Santos
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000068338:Everolimus; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D019459:Urothelium / Q000473:pathology
chemical_list: D000068338:Everolimus; D002945:Cisplatin; D020123:Sirolimus