Integrins are heterodimeric transmembrane receptors involved in a wide range of cancer cell activities. Cilengitide is a selective and potent inhibitor of αv integrins that blocks the ligation of αvβ3 and αvβ5 integrins to provisional matrix proteins[5]. The IC50 values of cilengitide against αvβ3 and αvβ5 are 4.1 nM and 79 nM, respectively[6]. In primary human brain capillary endothelial cells (BCECs), incubation with 1 μg/mL cilengitide for 1h decreased cell adhesion to vitronectin. When cilengitide was added 1h after the attachment of BCECs to vitronectin, the detachment occurred in a dose-dependent manner, and the significant detachment was observed at the concentration of 10 μg/mL or higher. In αv-integrin-expressing tumor cell lines U87MG and DAOY, the exposure of 25 μg/ml cilengitide for 24h led to a significant increase in apoptosis compared to cells treated with control peptide. In a mouse xenograft model established by injecting αv-positive melanoma cells into the forebrain, Cilengitide treatment resulted in an average survival of 36.5 days compared to 17.3 days in the control peptide-treated animals[7].
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