Changes in expression of genes encoding antioxidant enzymes, heme oxygenase-1, Bcl-2, and Bcl-xl and in level of reactive oxygen species in tumor cells resistant to doxorubicin

The relationship between expression of genes encoding key antioxidant enzymes, heme oxygenase-1, Bcl-2, and Bcl-xl and change in production of reactive oxygen species (ROS) resulting from development of resistance of cancer cells K562, MCF-7, and SKOV-3 to the prooxidant chemotherapeutic agent doxorubicin (DOX) has been studied. Significant increase in mRNA level and activity of Mn-superoxide dismutase (Mn-SOD), catalase, and selenium-dependent glutathione peroxidase-1 (GPx-1) and reduced ROS level was found in resistant K562/DOX and SKVLB cells. In contrast, no change in ROS level was observed in MCF-7/DOX cells in parallel with decrease in Mn-SOD and catalase mRNAs and corresponding activities concurrently with high increase in GPx-1 mRNA and activity. As a result of the development of resistance, a similarity was found between the change in ROS level and the change in ho-1 and bcl-2 gene expression, whereas elevation of bcl-xl gene expression was observed in all three types of resistant cells. Particular features of development of adaptive antioxidant response as well as redox-dependent change in bcl-2 gene expression under formation of DOX resistance of cancer cells of different genesis are discussed. © Nauka/Interperiodica 2006.

Kalinina E.V. 1, 2 , Chernov N.N. 3 , Saprin A.N. 1 , Kotova Ya.N.1 , Andreev Ya.A.4 , Solomka V.S.1 , Scherbak N.P.5
Номер выпуска
  • 1 Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, ul. Kosygina 4, 119991 Moscow, Russian Federation
  • 2 Institute of Cytochemistry and Molecular Pharmacology, ul. 6-ya Radialnaya 24/14, 115404 Moscow, Russian Federation
  • 3 Российский университет дружбы народов
  • 4 Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Mikluho-Maklaya 16/10, 117997 Moscow, Russian Federation
  • 5 Institute of Carcinogenesis, Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe Shosse 24, 115478 Moscow, Russian Federation
Ключевые слова
Antioxidant enzymes; Bcl-2; Bcl-xl; Doxorubicin; Drug resistance of cancer cells; Heme oxygenase-1; Reactive oxygen species
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