Novel treatment of ovarian cancer cell lines with Imatinib mesylate combined with Paclitaxel and Carboplatin leads to receptor-mediated antiproliferative effects.
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.
Mundhenke
Christoph
C
Department of Obstetrics and Gynecology, Campus Kiel, University of Kiel, Michaelisstrasse 16, 24105 Kiel, Germany.
Weigel
Marion Tina
MT
Sturner
Klarissa Hanja
KH
Roesel
Frank
F
Meinhold-Heerlein
Ivo
I
Bauerschlag
Dirk O
DO
Schem
Christian
C
Hilpert
Felix
F
Jonat
Walter
W
Maass
Nicolai
N
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
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