Molecular mechanisms of combretastatin A-4 amino sugar derivative CPU-XT-008 on inhibiting proliferation of vascular endothelial cells
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Graphical Abstract
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Abstract
Taking human umbilical vein endothelial cells(HUVEC)as experimental model which can simulate tumor-derived vascular endothelial cells, the effects of CPU-XT-008, an amino sugar derivative of combretastatin A-4(CA-4), on HUVEC proliferation, cell cycle distribution, tubulin polymerization and the key regulatory protein of cell cycle were studied. The effect of CPU-XT-008 on the proliferation of HUVEC was determined by MTT assay. The cell cycle distribution caused by CPU-XT-008 was detected by flow cytometry. Immunofluorescence was used to detect apoptosis and tubulin polymerization. The expressions of Cyclin B1, Cdc2 and β-tubulin were detected by Western blotting. Results demonstrated that CPU-XT-008 could target tubulin and inhibit the polymerization of β-tubulin, and it could lead to G2/M cell cycle arrest in HUVEC by up-regulating Cyclin B1 expression and down-regulating Cdc2 and p-Cdc2 expression, which resulted in inhibiting the proliferation of HUVEC and inducing its apoptosis.
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