Abstract
Purpose:
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma, Mucinous / drug therapy
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Adenocarcinoma, Mucinous / metabolism
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Adenocarcinoma, Mucinous / pathology
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Apoptosis / drug effects*
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Benzamides
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Carboplatin / administration & dosage
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Carcinoma, Papillary / drug therapy
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Carcinoma, Papillary / metabolism
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Carcinoma, Papillary / pathology
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Cell Proliferation / drug effects*
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Cystadenocarcinoma, Serous / drug therapy
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Cystadenocarcinoma, Serous / metabolism
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Cystadenocarcinoma, Serous / pathology
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Endometrial Neoplasms / drug therapy
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Endometrial Neoplasms / metabolism
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Endometrial Neoplasms / pathology
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Female
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Humans
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Imatinib Mesylate
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Immunoenzyme Techniques
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Ovarian Neoplasms / drug therapy*
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Ovarian Neoplasms / metabolism
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Ovarian Neoplasms / pathology
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Paclitaxel / administration & dosage
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Piperazines / administration & dosage
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Proto-Oncogene Proteins c-abl / genetics
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Proto-Oncogene Proteins c-abl / metabolism
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Proto-Oncogene Proteins c-kit / genetics
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Proto-Oncogene Proteins c-kit / metabolism
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Pyrimidines / administration & dosage
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Neoplasm / genetics
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RNA, Neoplasm / metabolism
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Receptor, Platelet-Derived Growth Factor alpha / genetics
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Receptor, Platelet-Derived Growth Factor alpha / metabolism*
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Receptor, Platelet-Derived Growth Factor beta / genetics
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Receptor, Platelet-Derived Growth Factor beta / metabolism*
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Tissue Array Analysis
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Tumor Cells, Cultured
Substances
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Benzamides
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Piperazines
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Pyrimidines
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RNA, Messenger
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RNA, Neoplasm
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Imatinib Mesylate
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Carboplatin
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Proto-Oncogene Proteins c-kit
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Receptor, Platelet-Derived Growth Factor alpha
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Receptor, Platelet-Derived Growth Factor beta
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Proto-Oncogene Proteins c-abl
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Paclitaxel