The integrin-linked kinase (ILK) is an intracellular serine/threonine kinase highly expressed in normal pancreatic, cardiac and skeletal muscle tissues. It plays an essential role in integrin and growth factor receptor-related signaling pathways. Targeted inhibition of ILK in cancer cells may reduce tumor growth. ILK-IN-3 (also known as QLT0267) is a small-molecule ILK inhibitor. The ED values of ILK-IN-3 for the inhibition of the viability of human breast tumor cell lines were 9.8 - 55.8μM. In both LCC6 and LCC6Her2 cells, treatment with ILK-IN-3 (0.3 - 42.67μM) alone or in combination with docetaxel reduced P-AKT (Ser473) levels in a dose-dependent manner. Treatment of LCC6 and LCC6Her2 cells with ILK-IN-3 at a concentration of 10μM led to a ~79% and ~83% decrease in VEGF secretion, respectively. In MCF-7Her2 cells, combined treatment with ILK-IN-3 (10μM) and docetaxel (0.25 nM) for 72 hours significantly reduced VEGF secretion compared with the control group. The combined therapy of ILK-IN-3 (200mg/kg, oral administration) and docetaxel (5mg/kg, intravenous administration) for 4 weeks reduced tumor burden and extended survival in mice implanted orthotopically with LCC6 breast cancer cells[2].
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