Redox-Dependent Expression of Genes Encoding NADPH Oxidase 5 and the Key Antioxidant Enzymes during Formation of Drug Resistance of Tumor Cells to Cisplatin

E V Kalinina; Y A Andreev; A S Petrova; K I Lubova; A A Shtil'; N N Chernov; M D Novichkova; N K Nurmuradov

doi:10.1007/s10517-018-4240-5

Redox-Dependent Expression of Genes Encoding NADPH Oxidase 5 and the Key Antioxidant Enzymes during Formation of Drug Resistance of Tumor Cells to Cisplatin

Bull Exp Biol Med. 2018 Sep;165(5):678-681. doi: 10.1007/s10517-018-4240-5. Epub 2018 Sep 17.

Authors

E V Kalinina¹, Y A Andreev², A S Petrova³, K I Lubova², A A Shtil'⁴, N N Chernov³, M D Novichkova³, N K Nurmuradov³

Affiliations

¹ Peoples' Friendship University of Russia, Moscow, Russia. elena.v.kalinina@gmail.com.
² M. M. Shemyakin and Yu. A. Ovchinnikov of Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
³ Peoples' Friendship University of Russia, Moscow, Russia.
⁴ N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, Russia.

PMID: 30225719
DOI: 10.1007/s10517-018-4240-5

Abstract

Expression of genes that plays a significant role in the control of cellular redox homeostasis was studied during the development of drug resistance of human ovarian adenocarcinoma SKOV-3 cells to cisplatin. It was found that the development of drug resistance was accompanied by enhanced expression of the genes encoding the key antioxidant enzymes (SOD2, CAT, GPX1, and HO-1) and transcription factor Nrf2, as well as reduced expression of the gene encoding NOX5 isoform of NADPH oxidase. The results testify to redox-dependent development of the adaptive antioxidant response as an important process in the mechanism of formation of resistance to cisplatin.

Keywords: NADPH oxidase 5; antioxidant enzymes; cisplatin; drug resistance of tumor cells; gene expression.

MeSH terms

Antineoplastic Agents / pharmacology*
Catalase / genetics
Catalase / metabolism
Cell Line, Tumor
Cisplatin / pharmacology*
Drug Resistance, Neoplasm / genetics*
Female
Gene Expression Regulation, Neoplastic*
Glutathione Peroxidase / genetics
Glutathione Peroxidase / metabolism
Glutathione Peroxidase GPX1
Heme Oxygenase-1 / genetics
Heme Oxygenase-1 / metabolism
Homeostasis
Humans
NADPH Oxidase 5 / antagonists & inhibitors
NADPH Oxidase 5 / genetics*
NADPH Oxidase 5 / metabolism
NF-E2-Related Factor 2 / agonists
NF-E2-Related Factor 2 / genetics*
NF-E2-Related Factor 2 / metabolism
Ovary
Oxidation-Reduction
Signal Transduction
Superoxide Dismutase / genetics
Superoxide Dismutase / metabolism

Substances

Antineoplastic Agents
NF-E2-Related Factor 2
NFE2L2 protein, human
Catalase
Glutathione Peroxidase
HMOX1 protein, human
Heme Oxygenase-1
Superoxide Dismutase
superoxide dismutase 2
NADPH Oxidase 5
NOX5 protein, human
Cisplatin
Glutathione Peroxidase GPX1
GPX1 protein, human