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  • Title: Combined antiproliferative activity of imatinib mesylate (STI-571) with radiation or cisplatin in vitro.
    Author: Yerushalmi R, Nordenberg J, Beery E, Uziel O, Lahav M, Luria D, Fenig E.
    Journal: Exp Oncol; 2007 Jun; 29(2):126-31. PubMed ID: 17704745.
    Abstract:
    UNLABELLED: Little is known about the interaction of novel anticancer drugs with other treatment modalities. THE AIM of this study was to examine the effect of combining imatinib mesylate (STI-571) with radiation or cisplatin on the survival of two human solid tumor cell lines - SKNMC cells derived from Ewing sarcoma and breast cancer MCF-7 cells. METHODS: Cell proliferation was determined using the sulphorodamine B cytotoxicity assay. Cell cycle analysis was performed with flow cytometry. Apoptosis was determined using a commercial cell death ELISA plus kit. Phosphorylated AKT, which has been suggested to be involved in radiation resistance, was detected by Western blot analysis. RESULTS: Exposure of SKNMC cells to STI-571 resulted in a dose-dependent antiproliferative effect and a decrease in phosphorylated AKT expression. There was no evidence of apoptosis. The combination of STI-571 with radiation or cisplatin had an additive antiproliferative effect in SKNMC cells (60% reduction in cell number). A similar effect was observed in human MCF-7 breast cancer cells. CONCLUSION: STI-571 improves the outcome of cisplatin or irradiation treatment in vitro. AKT pathway may play a role in the additive effect of STI-571 and irradiation.
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