title: Novel treatment of ovarian cancer cell lines with Imatinib mesylate combined with Paclitaxel and Carboplatin leads to receptor-mediated antiproliferative effects.
abstract: OBJECTIVE
  Imatinib is a small molecule inhibiting the tyrosine kinases bcr-abl, c-kit, PDGFR-alpha and PDGFR-beta. Investigations were performed to screen ovarian cancer cell lines and tumor samples for target receptor expression. Effects of Imatinib on cell proliferation and apoptosis induction were measured with and without additional cytotoxic agents.
  
  
  METHODS
  Expression patterns of abl, c-kit, PDGFR-alpha and PDGFR-beta (Imatinib targets) were studied in 5 cell lines and 111 tissue arrays by PCR and immunohistochemistry. Proliferation assays were performed with single agent Imatinib or combined with Paclitaxel and Carboplatin. Apoptosis was measured by DNA fragmentation.
  
  
  RESULTS
  All cell lines expressed abl and PDGFR-beta. C-kit was only expressed in 2/5 cell lines and PDGFR-alpha in 4/5. Imatinib reduced cell growth and lead to pro-apoptotic changes. Combination of Carboplatin, Paclitaxel and Imatinib showed synergistic activity.
  
  
  CONCLUSIONS
  Our results suggest that Imatinib may be useful for the specific treatment of ovarian cancer as an add-on to conventional chemotherapy.
authors.affiliation: Department of Obstetrics and Gynecology, Campus Kiel, University of Kiel, Michaelisstrasse 16, 24105 Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Mundhenke
authors.forename: Marion Tina
authors.initials: MT
authors.lastname: Weigel
authors.forename: Klarissa Hanja
authors.initials: KH
authors.lastname: Sturner
authors.forename: Frank
authors.initials: F
authors.lastname: Roesel
authors.forename: Ivo
authors.initials: I
authors.lastname: Meinhold-Heerlein
authors.forename: Dirk O
authors.initials: DO
authors.lastname: Bauerschlag
authors.forename: Christian
authors.initials: C
authors.lastname: Schem
authors.forename: Felix
authors.initials: F
authors.lastname: Hilpert
authors.forename: Walter
authors.initials: W
authors.lastname: Jonat
authors.forename: Nicolai
authors.initials: N
authors.lastname: Maass
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides; D016190:Carboplatin / Q000008:administration & dosage; D002291:Carcinoma, Papillary / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007124:Immunoenzyme Techniques; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000068877:Imatinib Mesylate; D016190:Carboplatin; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D016315:Proto-Oncogene Proteins c-abl; D017239:Paclitaxel