title: The effect of cilengitide in combination with irradiation and chemotherapy in head and neck squamous cell carcinoma cell lines.
abstract: BACKGROUND
  Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors under clinical evaluation, cilengitide is the most promising compound. However, little is known about the cellular processes induced during cilengitide therapy in combination with irradiation and cisplatin in head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  The cytostatic effect of cilengitide was assessed by proliferation assay in the three HNSCC cell lines SCC25, FaDu and CAL27. Combination experiments with cisplatin and irradiation were performed. Possible synergistic effects were calculated in combination index (CI) analyses. Colony forming inhibition was investigated in clonogenic assays. Real-time PCR arrays were used to evaluate target protein gene expression patterns. Flow cytometry was used to detect apoptosis.
  
  
  RESULTS
  Used alone, cilengitide has only minor cytotoxic effects in HNSCC cell lines. However, combination with cisplatin resulted in synergistic growth inhibition in all three cell lines. Irradiation showed synergism in short-term experiments and in colony forming assays, an additive effect was detected. Real-time PCR assay detected downregulation of the antiapoptotic protein Bcl-2 after exposure of cells to cilengitide.
  
  
  CONCLUSIONS
  Cilengitide in combination with cisplatin and irradiation may be a feasible option for the treatment of patients with head and neck cancer. However, further investigations are required to understand the exact mechanism that leads to synergistic cytotoxicity.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Heiduschka
authors.forename: C
authors.initials: C
authors.lastname: Lill
authors.forename: S
authors.initials: S
authors.lastname: Schneider
authors.forename: R
authors.initials: R
authors.lastname: Seemann
authors.forename: G
authors.initials: G
authors.lastname: Kornek
authors.forename: R
authors.initials: R
authors.lastname: Schmid
authors.forename: U
authors.initials: U
authors.lastname: Kotowski
authors.forename: D
authors.initials: D
authors.lastname: Thurnher
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors; D010039:Otorhinolaryngologic Neoplasms / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012910:Snake Venoms / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; D016023:Integrins; D019253:Proto-Oncogene Proteins c-bcl-2; D012910:Snake Venoms; C422910:Cilengitide; D002945:Cisplatin