Effect of a heat shock protein 90-specific inhibitor on the proliferation and apoptosis induced by VEGF-C in cervical cancer cells
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Authors
DU, XUE
LI, YONGMEI
JING, XU
ZHAO, LINA
Issue Date
2014-08-22
Type
Article
Language
en_US
Keywords
Cervical Cancer , Heat Shock Protein 90 , Vascular Endothelial Growth Factor-C , Proliferation , Apoptosis
Alternative Title
Abstract
The aim of the present study was to investigate the effect of heat shock protein 90 (Hsp90)-specific inhibitor geldanamycin (GA) on the proliferation and apoptosis induced by vascular endothelial growth factor-C (VEGF-C) in cervical cancer cells. HeLa cells (1×106/ml) in the logarithmic growth phase were incubated without serum for 24 h. The cells were pretreated with kinase insert domain receptor antibody (KDR)-Ab (20 μg/ml), phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (3 μmol/l), mitogen-activated protein kinase (MAPK) inhibitor PD98059 (30 μmol/l) or Hsp90-specific inhibitor GA (10 μmol/l) for 30 min, and then treated with VEGF-C (50 ng/μl) for a further 24 h. The cells were harvested for MTT analysis, annexin V-FITC/propidium iodide double staining for early apoptosis and SDS-PAGE and western blot analysis in order to determine Hsp90, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cyclin D1 expression. Treatment with VEGF-C alone induced Hsp90 protein expression in HeLa cells at all time-points. Hsp90 expression was increased 3.31-fold in VEGF-C treated HeLa cells, and this increase was attenuated in the treatment groups (2.17-, 1.69-, 1.82-fold in VEGF-C + KDR-Ab, VEGF-C + PD98059 and VEGF-C + LY294002, respectively). The proliferation of the VEGF-C-treated HeLa cells was increased ~2.13-fold, while that of the VEGF-C + GA-treated HeLa cells decreased 0.87-fold (P<0.05). Even low concentrations of GA (0.02 μmol/l) were found to inhibit the Bcl-2 and cyclin D1 protein expression induced by VEGF-C. Therefore, the results indicate that the Hsp90-specific inhibitor GA has a critical role in the proliferation and apoptosis induced by VEGF-C in cervical cancer cells.
Description
Citation
DU, X., Li, Y., Jing, X., & Zhao, L. (2014). Effect of a heat shock protein 90-specific inhibitor on the proliferation and apoptosis induced by VEGF-C in cervical cancer cells. Experimental and therapeutic medicine, 8(5), 1559–1564. https://doi.org/10.3892/etm.2014.1930
Publisher
Experimental and Therapeutic Medicine