Comparative 2D-DIGE proteomic analysis of ovarian carcinoma cells: Toward a reorientation of biosynthesis pathways associated with acquired platinum resistance

Ovarian cancer is the fifth most frequent cause of cancer death in women. Emergence of chemoresistance in the course of treatments with platinum drugs is in part responsible for therapeutic failures. In order to improve the understanding of the complex mechanisms involved in acquired platinum chemoresistance, we decided to compare the basal protein expression profile of the platinum-sensitive cell line OAW42 and that of its resistant counterpart OAW42-R by a proteomic approach. Reversed-phase HPLC pre-fractionated extracts from both cell lines were subjected to 2D-DIGE coupled to mass spectrometry (MS). Forty eight differentially expressed proteins were identified, 39 being up-regulated and 19 down-regulated in OAW42-R versus OAW42 cells. From the current knowledge on biological activities of most differentially expressed proteins, it can be inferred that the acquisition of resistance was associated with a global reorganization of biochemical pathways favoring the production of precursors for biosynthesis, and with the mobilization of macromolecule quality control mechanisms, preserving RNA and protein integrity under damage-inducing conditions.

Emergence of chemoresistance in the course of treatments with platinum drugs is in part responsible for therapeutic failure. To better understand mechanisms of cisplatin resistance, a comparative proteomic approach based on 2D-DIGE coupled to MS was applied to reversed-phase HPLC pre-fractionated proteins extracts from ovarian carcinoma cell lines, OAW42 and its CDDP-resistant counterpart, OAW42-R. We focused on differentially expressed proteins between these two cell lines and their implication toward biosynthesis pathways reorientation associated with acquired platinum resistance.Figure optionsDownload high-quality image (114 K)Download as PowerPoint slideHighlights
► We compare the protein expression profile of resistant versus sensitive ovarian cell lines by 2D-DIGE.
► 48 differentially expressed proteins were identified.
► Most of them are involved in several biochemical pathways.
► Several enzymes of these pathways may constitute targets to restore CDDP-sensitivity in ovarian carcinoma cells.