Expression of dihydrodiol dehydrogenase and resistance to chemotherapy and radiotherapy in adenocarcinoma cells of lung

Background: The cytoplasmic enzyme dihydrodiol dehydrogenase (DDH) plays an important role in the detoxification process. Recently, the overexpression of DDH was detected in non-small cell lung cancer (NSCLC) cells and patients with DDH overexpression were shown to have a significantly higher incidence of early tumor recurrence and distant metastasis. In this study, the correlation between DDH expression and resistance to cisplatin, adriamycin and radiotherapy in NSCLC was examined. Materials and Methods: Seven lung adenocarcinoma cell lines (H23, H838, H1437, H1648, H2009, H2087 and H2126) were used in the study. The DDH level was determined by reverse transcription polymerase chain reaction and immunoblotting. Drug- and radiation-mediated cytotoxicity was measured by clonogenic assay. DDH isoforms (DDH1, DDH2 and DDH3) were transfected into H23 cells that did not express DDH to examine their effects on drug and radiation resistance. Results: DDH-overexpressed adenocarcinoma cells exhibited a much higher resistance to doxorubicin, cisplatin and irradiation than cells with lower DDH expression. The DDH2- and DDH1-transfectants showed higher drug and radiation resistance than the DDH3-trasnfectant. Conclusion: Resistance to both anticancer drugs and irradiation in lung adenocarcinoma cells was closely associated with DDH activity. DDH1 and DDH2 were the main isoforms responsible for these effects.