title: In vitro radiosensitisation by trabectedin in human cancer cell lines.
abstract: OBJECTIVE
  To examine the potential radiosensitising properties of trabectedin (ET-743, Yondelis).
  
  
  METHODS
  In vitro chemosensitivity was assessed in four tumour cell lines (DU145, HeLa, HT29, HOP62) by the crystal violet method. IC10s and IC50s were established for 1-h, 24-h and 7-day (continuous) exposure times. Radiosensitisation was evaluated by conventional colony assay. BrdUrd DNA-labelling and flow cytometry were used to analyse cell cycle kinetics. The rate of apoptotic induction was assed by annexyn-V labelling.
  
  
  RESULTS
  Mean IC50s were 18.8 nM (10.5 - 30), 2.5 nM (1.5 - 5) and 0.25 nM (0.2-0.8) for 1 h, 24 h and continuous exposure times, respectively. HT29 and HOP62 were the most sensitive cells lines to trabectedin. Radiosensitisation was observed in DU145 and HeLa cells with a dose enhancement factor (DEF) of 1.92 and 1.77 at IC50 dose level, respectively. Trabectedin induced early S phase arrest in all cell lines studied.
  
  
  CONCLUSIONS
  Trabectedin, at pharmacologically appropriated concentrations, harbours a significant in vitro radiosensitising effect and induces cell cycle changes and apoptosis in several human cancer cell lines. Further studies to define the clinical potential of the combination of trabectedin and radiotherapy are needed.
authors.affiliation: Department of Radiation Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain. jromero.hpth@salud.madrid.org
authors.forename: Jesús
authors.initials: J
authors.lastname: Romero
authors.forename: Irma
authors.initials: I
authors.lastname: Zapata
authors.forename: Sofía
authors.initials: S
authors.lastname: Córdoba
authors.forename: José María
authors.initials: JM
authors.lastname: Jimeno
authors.forename: José Antonio
authors.initials: JA
authors.lastname: López-Martín
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Tercero
authors.forename: Alejandro
authors.initials: A
authors.lastname: De La Torre
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Vargas
authors.forename: Rafael
authors.initials: R
authors.lastname: Molerón
authors.forename: Ricardo
authors.initials: R
authors.lastname: Sánchez-Prieto
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D004149:Dioxoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D005434:Flow Cytometry; D019073:HT29 Cells / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D044005:Tetrahydroisoquinolines / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077606:Trabectedin; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D011838:Radiation-Sensitizing Agents; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin