P-17 - Expression of genes encoding NΑΔΗ−oxidase 5 and key antioxidant enzymes under formation of cancer cell resistance to cisplatin

Abstract

The important role in the maintenance of redox homeostasis is played by the ratio of ROS generation and catabolism catalyzed by enzymes whose imbalance can lead to an increase in the intracellular level of ROS and the development of some pathologies including cancer. Here we studied expression of genes, which involve in the control of the cellular redox state, under the development of resistance of human ovarian carcinoma SKOV-3 cell to cisplatin; its cytostatic effect is associated in a great part with prooxidant effect. It was found that the formation of cancer cell resistance was accompanied by an increase in the expression of genes encoding key antioxidant enzymes (SOD2, CAT, GPX1, HO-1) in parallel with a significant decrease in expression of the NOX5 gene, which controls one of major sources of ROS. The coordinated character of changes in the expression of genes can be promoted by enhanced expression of transcription factor Nrf2 in addition with the growth of GSH/GSSG ratio. The obtained results testify to the redox-dependent development of the adaptive antioxidant response as an important process in the mechanism of formation of cancer cell resistance to cisplatin. Acknowledgements: The publication was prepared with the support of the “RUDN University Program 5–100”.