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.
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.
Authors: Ahmedin Jemal; Taylor Murray; Elizabeth Ward; Alicia Samuels; Ram C Tiwari; Asma Ghafoor; Eric J Feuer; Michael J Thun Journal: CA Cancer J Clin Date: 2005 Jan-Feb Impact factor: 508.702
Authors: K Satomura; A R Derubeis; N S Fedarko; K Ibaraki-O'Connor; S A Kuznetsov; D W Rowe; M F Young; P Gehron Robey Journal: J Cell Physiol Date: 1998-12 Impact factor: 6.384
Authors: Marion T Weigel; Linda Dahmke; Christian Schem; Dirk O Bauerschlag; Katrin Weber; Peter Niehoff; Maret Bauer; Alexander Strauss; Walter Jonat; Nicolai Maass; Christoph Mundhenke Journal: BMC Cancer Date: 2010-08-09 Impact factor: 4.430