350 rub
Journal №8 for 2012 г.
Article in number:
Redox-Dependent Change of Expression of Genes Encoding Isoforms of Peroxiredoxin in Cancer Cells Resistant to Doxorubicin
Keywords: peroxiredoxin cellular redox status gene expression drug resistance of cancer cells doxorubicin
Authors:
E.V. Kalinina, T.T. Berozov, N.N. Chernov, A.A. Shtil, V.A. Glasunova, О.М. Kuznetsova, Е.А. Riskina, А.А. Еfremova, М.М. Basharov, S.S. Padaryan, U.V. Dutikova, A.A. Markova
Abstract:
Combination of antioxidant properties and ability to regulate cellular signaling and proliferation, to protect protein structure as chaperones and to inhibit redox-dependent pathways of apoptosis activation demonstrate the important role of Se-independent peroxidases - peroxiredoxins (Prxs) in cellular defense system against oxidative stress. The aim of the research was a study of expression of genes encoding Prx isoforms 1, 2, 6 under development of cancer cell resistance to doxorubicin (DOX) which has cytotoxic effect related not only with DNA intercalation but also with activation of ROS production. The cell lines were used in the study: human erythroleukemia K562, human breast carcinoma MCF-7 and human ovarian carcinoma SKOV-3 - DOX-sensitive cells (K562/S, MCF-7/S, SKOV-3 с IC50 - 0,35, 1,1, 0,2 µМ respectively) and DOX-resistant cells (K562/DOX, MCF-7/DOX, SKVLB с IC50 - 5,2, 25, 1,6 µМ respectively). Level of mRNA was determined using qRT-PCR. Electrophoresis of PCR products was conducted in 1,5-2 % agarose gel followed by densitometry. Gel analysis was performed using the BioCaptMW software (Vilber Lourmat). Maintenance of reduced glutathione (GSH) and its oxidative form (GSSG) were estimated by spectrophotometry assays. Growth of expression of PRDX6 gene was found in DOX-resistant K562/DOX, MCF-7/DOX, SKVLB cells whereas an increase of expression of PRDX1 и PRDX2 genes was detected only in SKVLB cells. Elevation of GSH/GSSG was observed in all three types of resistant cells. The data indicate that the enhancement of expression of genes encoding Prx isoforms 1, 2, 6 has redox-dependent character which counts in favour of the important role of redox-dependent mechanism of development of the cancer cells resistance to DOX. Enhancement of expression of genes encoding Prx isoforms 1, 2, 6 has redox-dependent character associated with cell specificity. The data indicate the important role of redox-dependent mechanism of development of the cancer cells resistance to DOX.
Pages: 27-33
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