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Imatinib mesylate presents a cytostatic effect on B16 cells in vitro and an apoptotic outcome in melanoma in vivo.
Author(s) -
Pirraco Ana,
Coelho Pedro,
Rocha Ana,
Costa Raquel,
Soares Raquel
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.625.14
Subject(s) - imatinib mesylate , imatinib , in vivo , autocrine signalling , apoptosis , paracrine signalling , cancer research , platelet derived growth factor receptor , melanoma , in vitro , cell growth , tyrosine kinase inhibitor , growth factor , pharmacology , chemistry , medicine , receptor , biology , biochemistry , cancer , microbiology and biotechnology , myeloid leukemia
Melanoma is characterised by a general expression of platelet‐derived growth factor (PDGF) and its cognate receptor and by the down‐regulation of c‐Kit as the malignant potential increases. PDGF is also a powerful growth factor with autocrine and paracrine effects within melanoma. Both receptors are protein tyrosine kinases shown to be inhibited by imatinib mesylate. The aim is to investigate the effect of imatinib in melanoma cells in vitro and in vivo . Culture of B16 cells were incubated with imatinib either in the presence or absence of recombinant PDGF‐AA and assayed for proliferation (BrdU incorporation assay), apoptosis (TUNEL assay) and invasion (Double‐Chamber assay). C57BL/6 mice injected subcutaneously with B16 cells were treated daily with 100mg/Kg imatinib mesylate (n=10) or saline solution (n=6) for 2wk. Paraffin‐embedded tumour tissues were analysed for proliferation and apoptosis. Results suggest that imatinib has an inhibitory effect on the proliferation and migration of melanoma cells with no significant increase in apoptosis. However, besides preventing proliferation, imatinib strongly induces apoptosis within the tumor. In conclusion, these distinct in vitro and in vivo findings suggest that tumor cell behaviour is influenced by the action of imatinib in the tumor microenvironment. (supported by Novartis Farma, Portugal)