P 092 - Coordinated alteration of expression of redox-dependent genes in development of adaptive antioxidant response under formation of drug resistance of cancer cells

Abstract

Aims Here we studied the expression of isoforms of redox-dependent antioxidant enzymes and a rise of adaptive antioxidant response under development of cancer cells resistance to anticancer agent cisplatin (CDDP) possessed pro-oxidant action. Results Under development of resistance of human erythroleukemia K562 and ovarian carcinoma SKOV-3 cells to CDDP co-ordinative enhanced expression of genes encoding isoforms of superoxide dismutase (SOD1, SOD2), glutathione peroxidase (GPx1, GPx4), glutathione transferase (GSTP1-1, GSTМ1-1), glutaredoxin (GLRX1, GLRX2), thioredoxin (TRX1,TRX2) was found in both types of resistant cells in compare with wild cells. In addition, growth of GSH/GSSG ratio as index of cellular redox state as well as elevated level of transcription factor Nrf2 were observed in resistant K562/DOX and SKVLB cells. Decrease of apoptotic cell death was observed under exposure to hydrogen peroxide in the CDDP-resistant cells possessed elevated antioxidant status, as evidenced by low generation of ROS. It can be concluded that the mechanism of the formation of cancer cells resistance to CDDP involves the development of adaptive antioxidant response as key in stress adaptation.