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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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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.

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Acknowledgment

We are thankful for an unrestricted research grant from Novartis Pharmaceutical, Germany supporting this study.

Author information

Correspondence to Marion Tina Weigel.

Additional information

C. Mundhenke and M. T. Weigel contributed equally to this work.

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Mundhenke, C., Weigel, M.T., Sturner, K.H. et al. Novel treatment of ovarian cancer cell lines with Imatinib mesylate combined with Paclitaxel and Carboplatin leads to receptor-mediated antiproliferative effects. J Cancer Res Clin Oncol 134, 1397 (2008). https://doi.org/10.1007/s00432-008-0408-0

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Keywords

  • Ovarian cancer
  • Targeted therapy
  • In vitro
  • Imatinib Mesylate