title: A proteomic approach to paclitaxel chemoresistance in ovarian cancer cell lines.
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.
authors.affiliation: John Paul II Centre for High Technology Researches and Education in Biomedical Sciences, Catholic University, Campobasso, Italy. michela.dimichele@moli-sani.org
authors.forename: Michela
authors.initials: M
authors.lastname: Di Michele
authors.forename: Anna
authors.initials: A
authors.lastname: Della Corte
authors.forename: Lucia
authors.initials: L
authors.lastname: Cicchillitti
authors.forename: Piero
authors.initials: P
authors.lastname: Del Boccio
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
authors.forename: Cristiano
authors.initials: C
authors.lastname: Ferlini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Maria Benedetta
authors.initials: MB
authors.lastname: Donati
authors.forename: Domenico
authors.initials: D
authors.lastname: Rotilio
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology*; D020543:Proteome / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020543:Proteome; D017239:Paclitaxel