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.