Discovery and Validation of Biomarkers of Cisplatin Resistance in Human Ovarian Cancer Using Proteom

来源 :BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会) | 被引量 : 0次 | 上传用户:liuwu521
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  Platinum-based chemotherapy, such as cisplatin, is the primary treatment for ovarian cancer.However, drug resistance has become a major impediment to the successful treatment of ovarian cancer.To date, the molecular mechanisms of resistance to platinum-based chemotherapy remain unclear.In this study, we applied a LC/MS-based, label-free, protein quantification method to examine the global protein expression profiles of two pairs of ovarian cancer cell lines, A2780/A2780-CP (cisplatin-sensitive/cisplatin-resistant) and 2008/2008-C 13*5.25 (cisplatin-sensitive/cisplatin-resistant).We identified and quantified over 2000 proteins from these cell lines and 95 proteins showed significant expression changes between sensitive and resistant groups with a false-discovery-rate (FDR) of less than 5%.Bioinformatics analysis suggested several potential pathways that may be involved in cisplatin resistance.Among these potential pathways, a redox regulated pathway involving superoxide dismutase 1 (SOD1) was targeted in order to further explore its involvement in drug resistance.SOD 1 represents a potential biomarker for early evaluation of drug resistance.Inhibition of SOD 1 activity enabled re-sensitization of the cisplatin resistant ovarian cancer cells.This study provides not only a new proteomic platform for large-scale quantitative protein analysis, but also important information for potential biomarkers of cisplatin resistance in ovarian cancer.Furthermore, these results may be clinically relevant for diagnostics, prognostics, and therapeutic improvement for ovarian cancer treatment.
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