Proteomic analysis of cisplatin resistance in ovarian cancer

Cisplatin [cis-diamminedichloroplatinum (II)] is one of the most potent and highly effective chemotherapeutic agents for treatment of several types of cancer including ovarian, cervical, and testicular cancers. However, the development of acquired resistance has limited its effectiveness, especially in ovarian cancer chemotherapy. Resistance to cisplatin is not completely understood and it is thought to occur through many different mechanisms. Therefore a great deal of investigation has concerned the ways to overcome drug resistance, including the development of new chemotherapeutic compounds, addition of translational agents which modify signal transduction pathways or investigation of new methods for drug administration. In the present study we search for protein networks associated with drug resistance by comparing protein expression in two human ovarian carcinoma cell lines one sensitive and the other resistant to cisplatin, respectively 2008 and C13* cells. The resistant subline, isolated after prolonged exposure to low drug doses, is approximately 20-fold more resistant to cisplatin than the sensitive one. Comparative analysis was performed by two-dimensional liquid chromatography system (chromatofocusing and reverse phase chrommatography). Forty four peaks showing a differential expression of at least 100% between the two cell lines where further analysed and identified by MALDI-TOF mass spectrometry. To obtain insights into potential cellular pathways that may be modified in two cell lines, an explorative in silico analysis was undertaken using IPA software. The most interesting network emerging from this analysis featured 17 of the 44 imported proteins and main functions associated with the components of this network, were gene expression and lipid metabolism. Moreover, analysis of biological function of differential protein show several proteins involved in Immunity and Stress response.