Differential effect of imatinib and synergism of combination treatment with chemotherapeutic agents in malignant glioma cells.

摘要: Imatinib mesylate (STI571, Gleevec) is a signal transduction inhibitor and novel anti-cancer agent. It selectively inhibits aberrantly activated tyrosine kinases in malignant cells, for example, bcr-abl leukaemia, platelet-derived growth factor receptor stem cell (c-Kit) solid cancers including glioma. However, recently published clinical studies with imatinib monotherapy patients glioma demonstrated only very modest anti-tumour activity. The aim of this study was to investigate the biological activity imatinib, its cellular mechanisms action synergism other chemotherapeutic agents human cells culture. Expression PDGF/R c-Kit analyzed by RT-PCR. Proliferation measured MTT assays drug synergy assessed Chou-Talalay method. Cell cycle apoptosis were flow cytometry migration monolayer assays. Multi-immunoblot performed on imatinib-treated control cells. Results indicate that more effective inhibiting colony formation rather than proliferation. treatment caused arrest G0-G1 or G2/M, significant elevation few cyclin-dependent kinases. Furthermore, acted synergistically chemotherapy agents, such as DNA alkylating agent, temozolomide, riboneucleotide reductase inhibitors, hydroxyurea at varied dose levels. In conclusion, exerts effects Synergistic interaction may be related could potentially important setting.