Overexpression of thioredoxin does not confer resistance to cisplatin in transfected human ovarian and colon cancer cell lines.
OBJECTIVE
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.
Yamada
M
M
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Tomida
A
A
Yoshikawa
H
H
Taketani
Y
Y
Tsuruo
T
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000473:pathology; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000473:pathology; D017382:Reactive Oxygen Species; D013879:Thioredoxins / Q000032:analysis* / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D002945:Cisplatin