【摘 要】
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The fibroblast growth factor receptors (FGFRs) are increasingly considered attractive targets for therapeutic cancer intervention due to their roles in tumor me
【机 构】
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Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Mat
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The fibroblast growth factor receptors (FGFRs) are increasingly considered attractive targets for therapeutic cancer intervention due to their roles in tumor metastasis and angiogenesis.Here,we identified a new selective FGFR inhibitor,C11,and assessed its antitumor activities.C11 was a selective FGFR1 inhibitor with an ICso of 19 nM among a panel of 20 tyrosine kinases.C11 inhibited cell proliferation in various tumors,particularly bladder cancer and breast cancer.C11 also inhibited breast cancer MDA-MB-231 cell migration and invasion via suppression of FGFR1 phosphorylation and its downstream signaling pathway.Suppression of matrix metalloproteinases 2/9 (MMP2/9) was associated with the anti-motility activity of C11.Furthermore,the anti-angiogenesis activity of C11 was verified in endothelial cells and chicken chorioallantoic membranes (CAMs).C11 inhibited the migration and tube formation of HMEC-1 endothelial cells and inhibited angiogenesis in a CAM assay.In sum,C11 is a novel selective FGFR1 inhibitor that exhibits potent activity against breast cancer metastasis and angiogenesis.
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