Molecular mechanisms of combretastatin A-4 amino sugar derivative CPU-XT-008 on inhibiting proliferation of vascular endothelial cells
10.11665/j.issn.1000-5048.20150513
- VernacularTitle:Combretastatin A-4氨基糖类衍生物 CPU-XT-008抑制血管内皮细胞增殖的分子机制
- Author:
Shuying HE
;
Rui XIONG
;
Kun LIU
;
Yungen XU
- Publication Type:Journal Article
- Keywords:
combretastatin A-4;
CPU-XT-008;
amino sugar derivative;
human umbilical vein endothelial cells;
tubulin;
cell cycle
- From:
Journal of China Pharmaceutical University
2015;(5):594-599
- CountryChina
- Language:Chinese
-
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 pro-tein 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 poly-merization ofβ-tubulin;and it could lead to G2/M cell cycle arrest in HUVEC by up-regulating Cyclin B1 expres-sion and down-regulating Cdc2 and p-Cdc2 expression;which resulted in inhibiting the proliferation of HUVEC and inducing its apoptosis.
