The Expression of Genes Encoding Antioxidant Enzymes in Lung Adenocarcinoma A549 Cells Exposed to Cisplatin Supplemented by Polyunsaturated Fatty Acids

作者：Zajdel Alicja^*; Wilczok Adam; Gruchlik Arkadiusz; Paduszynski Piotr; Dzierzewicz Zofia

来源：Advances in Clinical and Experimental Medicine, 2010, 19(5): 585-591.

• antioxidant enzymes
• PUFAs
• cisplatin
• A549 cells

Background. The effectiveness of cisplatin (CPT) in the treatment of tumors is often limited by primary or acquired resitance. Supplementation with polyunsaturated fatty acids, in particular eicosapentaenoic acid (EPA, 20 : 5, n-3) and docosahexaenoic acid (DHA, 22 : 6, n-3), can enhance drug sensitivity of tumor cells to anticancer therapy or reverse cell resistance. Antioxidant enzymes, highly expressed in lung tumors, are among the determinant factors in the sensitivity of lung tumors to chemotherapy.
Objectives. Investigation of the effect of EPA and DHA at different concentrations on gene expression of selected enzymes controlling cell redox status, such as superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), catalase (CAT), phospholipid hydroperoxide glutathione peroxidase (GPx-4), and glutathione S-transferase pi (GST-pi) in human lung adenocarcinoma cells (A549) exposed to CPT.
Material and Methods. Viability of A549 cells treated with CPT and EPA or DHA was measured using the XTT tetrazolium salt based assay. Expression of genes encoding the antioxidant enzymes was determined by quantitative reverse-transcription polymerase chain reaction (QRT-PCR) analysis after RNA isolation from A549 cells.
Results. EPA and DHA added to the culture medium, increased the antitumor activity of CPT in A549 cells in a concentration dependent manner. The SOD2 and GST-pi expression showed marked increase after CPT treatment, while supplementation with EPA and DHA down-regulated their expression in the CPT treated A549 cells. The observed changes in mRNA levels of CAT were not statistically significant.
Conclusions. The reduction of antioxidant potential in cancer cells may sensitize these cells to anticancer therapy. PUFAs supplementation during CPT-based anticancer therapy may enhance effectiveness of the treatment (Adv Clin Exp Med 2010, 19, 5, 585-591).

• 出版日期2010