Novel treatment of ovarian cancer cell lines with Imatinib mesylate combined with Paclitaxel and Carboplatin leads to receptor-mediated antiproliferative effects |
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Authors: | Christoph Mundhenke Marion Tina Weigel Klarissa Hanja Sturner Frank Roesel Ivo Meinhold-Heerlein Dirk O Bauerschlag Christian Schem Felix Hilpert Walter Jonat Nicolai Maass |
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Institution: | (1) Department of Obstetrics and Gynecology, Campus Kiel, University of Kiel, Michaelisstrasse 16, 24105 Kiel, Germany |
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Abstract: | Purpose Imatinib is a small molecule inhibiting the tyrosine kinases bcr-abl, c-kit, PDGFR-α and PDGFR-β. 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-α and PDGFR-β (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-β. C-kit was only expressed in 2/5 cell lines and PDGFR-α 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.
C. Mundhenke and M. T. Weigel contributed equally to this work. |
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Keywords: | Ovarian cancer Targeted therapy In vitro Imatinib Mesylate |
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