A proteomic approach to paclitaxel chemoresistance in ovarian cancer cell lines

Michela Di Michele, Anna Della Corte, Lucia Cicchillitti, Piero Del Boccio, Andrea Urbani, Cristiano Ferlini, Giovanni Scambia, Maria Benedetta Donati, Domenico Rotilio

Research output: Contribution to journalArticlepeer-review

Abstract

Ovarian cancer is the leading cause of gynaecological cancer mortality. Paclitaxel is used in the first line treatment of ovarian cancer, but acquired resistance represents the most important clinical problem and a major obstacle to a successful therapy. Several mechanisms have been implicated in paclitaxel resistance, however this process has not yet been fully explained. To better understand molecular resistance mechanisms, a comparative proteomic approach was undertaken on the human epithelial ovarian cancer cell lines A2780 (paclitaxel sensitive), A2780TC1 and OVCAR3 (acquired and inherently resistant). Proteins associated with chemoresistance process were identified by DIGE coupled with mass spectrometry (MALDI-TOF and LC-MS/MS). Out of the 172 differentially expressed proteins in pairwise comparisons among the three cell lines, 151 were identified and grouped into ten main functional classes. Most of the proteins were related to the category of stress response (24%), metabolism (22%), protein biosynthesis (15%) and cell cycle and apoptosis (11%), suggesting that alterations of those processes might be involved in paclitaxel resistance mechanisms. This is the first direct proteomic comparison of paclitaxel sensitive and resistant ovarian cancer cells and may be useful for further studies of resistance mechanisms and screening of resistance biomarkers for the development of tailored therapeutic strategies.

Original languageEnglish
Pages (from-to)225-236
Number of pages12
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1794
Issue number2
DOIs
Publication statusPublished - Feb 2009

Keywords

  • 2D-DIGE
  • Drug resistance
  • Ovarian cancer
  • Paclitaxel
  • Proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Analytical Chemistry
  • Molecular Biology

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