|Home | About | Journals | Submit | Contact Us | Français|
Ovarian Cancer is the fifth leading cause of death from all cancers in women. Platinum-based chemotherapy is the primary treatment for ovarian cancer. Most patients with the disease are initially very responsive to chemotherapeutic treatment. However, the majority of ovarian cancer patients eventually relapses and becomes refractory to additional treatment. This drug-resistance is a major impediment to the successful treatment of ovarian cancer. To date the mechanisms of drug-resistance are poorly understood. To elucidate the underlying mechanisms in which drug-resistance is developed in ovarian cancer cells, global protein expression pattern changes in drug-sensitive and -resistant ovarian cancer cells need to be established.
In this study, we approached ovarian cancer resistance using proteomics technology to quantitatively profile the global protein expression levels of two pairs of ovarian cancer cell lines, with cisplatin drug treatment. A2780 and 2008 human ovarian cancer cell lines were chosen as cisplatin-sensitive and A2780/CP and 2008/C13*5.25 were their resistant counterpart. Statistical analysis was carried out by ANOVA models and these were fit using Proc_Mixed in SAS. Through our efforts to identify those protein changes associated with cisplatin drug-resistance, we identified and quantified over ~2000 proteins where 855 proteins were identified with high confidence (Priority 1) and 760 of them showed significant expression changes (False Discovery Rate is less than 0.05). Based on the data that we obtained, we were able to select a panel of potential proteins that could play a role in cisplatin drug resistance. Inhibition assays targeting select proteins from our panel were carried out, to determine whether down-regulation of these proteins would be successful in reversing cisplatin resistance. Preliminary data showed a very promising effect in reversing the cisplatin resistance in the resistant cells when the combination of cisplatin and TETA, an inhibitor of antioxidant Superoxide dismutase (SOD1) protein, were used.