Trx/TrxR system in redox-dependent regulation under development of cisplatin resistance in cancer cells
Trx/TrxR-regulatory redox pathways may be the significant part of key events in the stress response and/or resetting redox homeostasis resulted in the change of most vital functions of cells, including proliferation, differentiation, apoptosis. Here we studied a level of Trx/TrxR activity and cellular redox-dependent changes during the development of resistance in human ovarian carcinoma SKOV-3 cells to cisplatin that possesses prooxidant effect. Increase of TRX1, TRXDR1, TRXDR2 gene expression as well as Trx and TrxR activity was found under formation of cancer cell resistance. The alteration of Trx/TrxR system was detected together with a change of the balance ROS/antioxidants in favor of growth of antioxidant state due to increase of key antioxidant enzymes gene expression (SOD2, CAT, GPX1, HO-1) and decrease of NADPH oxidase (NOX5) expression. Apoptosis suppression and much smaller extent of ASK1 and JNK1 phosphorylation were observed in resistant SKOV3/CDDP cells in contrast to the wild cells under H2O2 treatment. The results testify in favor of the important role of Trx/TrxR system in the rise of adaptive antioxidant response under formation of cisplatin resistance in cancer cells.
The publication was prepared with the support of the «RUDN University Program 5-100».