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.
Keywords Ovarian cancer - Targeted therapy - In vitro - Imatinib Mesylate
C. Mundhenke and M. T. Weigel contributed equally to this work.