Identification of Cisplatin-Resistance Associated Genes through Proteomic Analysis of Human Ovarian Cancer Cells and a Cisplatin-resistant Subline

Chemoresistance to cancer therapy is a major obstacle to the effective treatment of human cancers withcisplatin (DDP), but the mechanisms of cisplatin-resistance are not clear. In this study, we established a cisplatinresistanthuman ovarian cancer cell line (COC1/DDP) and identified differentially expressed proteins related tocisplatin resistance. The proteomic expression profiles in COC1 before and after DDP treatment were examinedusing 2-dimensional electrophoresis technology. Differentially expressed proteins were identified using matrixassistedlaser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and high performanceliquid chromatography-electrospray tandem MS (NanoUPLC-ESI-MS/MS). 5 protein spots, for cytokeratin 9,keratin 1, deoxyuridine triphosphatase (dUTPase), aarF domain containing kinase 4 (ADCK 4) and cofilin1,were identified to be significantly changed in COC1/DDP compared with its parental cells. The expression ofthese five proteins was further validated by quantitative PCR and Western blotting, confirming the results ofproteomic analysis. Further research on these proteins may help to identify novel resistant biomarkers or revealthe mechanism of cisplatin-resistance in human ovarian cancers.