[The effect of bortezomib on migration of endothelial cells and angiogenesis].
OBJECTIVE
To investigate the effects of bortezomib on the migration of endothelial cells and the expression of angiogenesis-related molecules, and explore the mechanism of its antiproliferation of tumor cells.


METHODS
Cell count kit CCK-8 was used to detect the relative proliferation activity of cells after treated by bortezomib at different concentrations for 12 h and 24 h, respectively. Transwell model was uesd to detect the migration rate of cells. Expression levels of VEGF and Annexin A2 genes were determined by real-time quantitative PCR. Annexin A2 protein was validated by Western blot.


RESULTS
After treated with bortezomib at concentrations of 2.5, 5.0 and 10 nmol/L for 12h, respectively, the HMEC-1 cell proliferation activity was 1.004 ± 0.002, 0.793 ± 0.021 and 0.874 ± 0.062, respectively, being no statistical difference from that of control group (1.000) P < 0.05); while the migration rates of them were 0.697 ± 0.060, 0.597 ± 0.090 and 0.874 ± 0.062, respectively, being significantly lower than that of control group (1.000) (P < 0.05) and so did for the expression of VEGF and Annexin A2 genes. After treated with 5 nmol/L bortezomib for 12 h, the Annexin A2 and VEGF gene relative expression level of HMEC-1 cells was 0.540 ± 0.001 and 0.793 ± 0.153, respectively, being of statistical difference from that of control group (1.000) P < 0.05). The conspicuous downregulation of Annexin A2 protein was also confirmed by Western Blot.


CONCLUSIONS
Bortezomib can inhibit migration of endothelial cell HMEC-1 by downregulating the expression of VEGF and Annexin A2, displaying a new mechanism of bortezomib for inhibition of tumor proliferation.
The First Hospital Affiliated Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hematasis, Ministry of Health, Suzhou 215006, China.
Lei-Xi
LX
Xue
Miao
M
Jiang
Li-Qian
LQ
Xie
Chang-Geng
CG
Ruan
D017306:Annexin A2 / Q000378:metabolism; D000069286:Bortezomib; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D017306:Annexin A2; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000069286:Bortezomib