Peroxiredoxin 6 and redox-dependent changes under development of cancer drug resistance

Among the peroxiredoxin family members peroxiredoxin 6 (Prx6) not only to reduce H2O2 and phospholipid hydroperoxides but also possesses phospholipase A2 and lysophosphatidylcholine acyl transferase activities which are different exchanged in some pathologies including cancer. However, contribution of Prx6 into the regulation of oxidant/antioxidant balance, that responsible for proliferation/apoptosis switching, under tumor growth is still poor understood. Here we studied PRX6 changes as well as cellular redox state during the formation of cisplatin resistance in human ovarian carcinoma SKOV-3 cells. The development of the drug resistance found to be accompanied by the increase of PRDX6 expression and growth of GSH/GSSG ratio due to elevation of GSH level, which needs for reduction of Prx6 oxidized form, as a result of enhancement of GSH synthesis de novo. In addition, it was established that siRNA knockdown of Trx1 increased CDDP-induced death of resistant cells that was significantly rose by additively use of siRNA knockdown of Prx6. The results testify to the important role of Prx6 in redox-dependent mechanism of cancer cell resistance to cisplatin. The publication was prepared with the support of the «RUDN University Program 5-100».