title: Synergistic cytotoxic activity of treosulfan and gemcitabine in pancreatic cancer cell lines.
abstract: BACKGROUND
  Treatment for advanced pancreatic cancer is still very unsatisfactory. Treosulfan is an alkylating agent used for conventional, as well as high-dose chemotherapy regimens, whereby plasma concentrations over 500 μg/ml can be achieved. We investigated the effects of treosulfan on pancreatic cancer cell lines.
  
  
  METHODS
  Using Panc-1, MIA PaCa-2 and Capan-2 cell lines, we investigated the in vitro cytotoxicity of treosulfan-alone and in combination with gemcitabine, 5-fluorouracil or irradiation.
  
  
  RESULTS
  Treosulfan was potently cytotoxic against all pancreatic cancer cell lines at all concentrations (1-100 μg/ml). Combination of treosulfan and gemcitabine revealed strong synergistic effects independent of the sequence of drug administration. Similarly, synergism was observed with irradiation. Combination of treosulfan and 5-fluorouracil revealed antagonism.
  
  
  CONCLUSIONS
  Treosulfan effectively kills pancreatic carcinoma cells in vitro and has synergistic activity in combination with gemcitabine and irradiation. These results warrant further investigation of treosulfan in the treatment of pancreatic cancer.
authors.affiliation: Clinic for Stem Cell Transplantation, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. ayuketan@uke.de.
authors.forename: Emilia
authors.initials: E
authors.lastname: Nitsch
authors.forename: Sormeh
authors.initials: S
authors.lastname: Mina
authors.forename: Ingo
authors.initials: I
authors.lastname: Brammer
authors.forename: Andrea
authors.initials: A
authors.lastname: Pace
authors.forename: Gunter
authors.initials: G
authors.lastname: Schuch
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Axel
authors.initials: A
authors.lastname: Zander
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Francis
authors.initials: F
authors.lastname: Ayuk
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D002066:Busulfan / Q000031:analogs & derivatives* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D010190:Pancreatic Neoplasms; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; C018404:treosulfan; D002066:Busulfan; D005472:Fluorouracil; D000093542:Gemcitabine
keywords: Treosulfan; gemcitabine; pancreatic cancer