title: Effect of a heat shock protein 90-specific inhibitor on the proliferation and apoptosis induced by VEGF-C in cervical cancer cells.
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.
authors.affiliation: Department of Obstetrics and Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: DU
authors.affiliation: Department of Microbiology and Immunology, Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biological Engineering, College of Life Sciences, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Jing
authors.affiliation: Department of Biological Engineering, College of Life Sciences, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhao
keywords: apoptosis; cervical cancer; heat shock protein 90; proliferation; vascular endothelial growth factor-C