Overexpression of thioredoxin does not confer resistance to cisplatin in transfected human ovarian and colon cancer cell lines

Abstract

Purpose: We have previously reported increased expression of thioredoxin (TRX) in cell lines with both acquired and intrinsic cisplatin (cDDP) resistance. We found that the expression levels of TRX correlate with cellular resistance to the drug. The purpose of this study was to elucidate whether TRX induces cDDP resistance in the absence of other intracellular changes. Methods: We developed cell lines stably expressing high levels of TRX by transfection of human ovarian cancer A2780 and colon cancer HT-29, and examined their sensitivity to cDDP. Results: The TRX transfectants expressed two- to threefold more TRX with corresponding activities than the parental cells or mock transfectants. TRX-transfected HT-29 cells expressed higher levels of TRX than cDDP-resistant variant cells. Both TRX-transfected A2780 and HT-29 cells showed no resistance to cDDP. Though TRX-transfected A2780 cells showed 1.8-fold increased resistance to H₂O₂, resistance to adriamycin and mitomycin C, which generate oxygen radicals, was not observed in the transfectants. Conclusions: These results suggest that TRX may be necessary but insufficient to induce resistance against cDDP as well as other chemotherapeutic drugs.