Proteomic analysis of anti-angiogenic effects by a combined treatment with vinblastine and rapamycin in an endothelial cell line

Natascia Campostrini, Danilo Marimpietri, Andrea Totolo, Carmine Mancone, Gian Maria Fimia, Mirco Ponzoni, Pier Giorgio Righetti

Research output: Contribution to journalArticle

Abstract

Angiogenesis controls the new blood supply routes into the tumor mass via the host endothelial cells (ECs). In this study, the EA.hy926 endothelial cell line has been treated with vinblastine (VBL) and rapamycin (RAP), both separately and in combination at low doses. Recently, we demonstrated the synergistic antiangiogenic effects of a combination of VBL and RAP at very low doses in vitro and in vivo. Herein, we confirm the ability of this combined treatment to statistically inhibit the proliferation of ECs, in a synergistic manner, by inducing apoptosis. The aim of this study was to substantiate these findings at the protein level. Differential proteomic analysis was performed on untreated control cells, treated with VBL, incubated with RAP, or subjected to a drug combination. Differentially expressed 113 polypeptide chains were visualized and 65 were identified via MALDI-TOF analysis. Some of the regulated proteins are involved in the processes of angiogenesis, proliferation, migration, and apoptosis. The down-modulation of ATP synthase, annexin A2, heat shock p70, glucose-6-phosphate dehydrogenase, vasodilator-stimulated phosphoprotein, proteasome 26S, tryptophanyl-tRNA synthetase, and stathmin/OP18, as well as the up-modulation of carbonyl reductase, Rho-GDI, and histone H1.0 correlates with the synergistic antiangiogenic activity of VBL and RAP.

Original languageEnglish
Pages (from-to)4420-4431
Number of pages12
JournalProteomics
Volume6
Issue number15
DOIs
Publication statusPublished - Aug 2006

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Vinblastine
Endothelial cells
Sirolimus
Proteomics
Endothelial Cells
Cell Line
rho-Specific Guanine Nucleotide Dissociation Inhibitors
Tryptophan-tRNA Ligase
Alcohol Oxidoreductases
Stathmin
Modulation
Annexin A2
Apoptosis
Glucosephosphate Dehydrogenase
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Drug Combinations
Histones
Tumors
Shock
Proteins

Keywords

  • Angiogenesis
  • Two-dimensional maps

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Proteomic analysis of anti-angiogenic effects by a combined treatment with vinblastine and rapamycin in an endothelial cell line. / Campostrini, Natascia; Marimpietri, Danilo; Totolo, Andrea; Mancone, Carmine; Fimia, Gian Maria; Ponzoni, Mirco; Righetti, Pier Giorgio.

In: Proteomics, Vol. 6, No. 15, 08.2006, p. 4420-4431.

Research output: Contribution to journalArticle

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