Synergistic effect of peroxiredoxin II antisense on cisplatin-induced cell death.
Peroxiredoxin II (Prx II) is known not only to protect cells from oxidative damage caused by hydrogen peroxide (H202), but also to endow cancer cells with resistance to both H202 and cisplatin and to grant them radioresistance. In this study, we examined whether Prx II antisense could enhance cisplatin-induced cell death. When gastric cancer cells were transfected with various concentrations of Prx II antisense plasmid, pPrxII/AS, and then treated with the same concentrations of cisplatin, Prx II antisense enhanced cisplatin-induced cell death. The combination index (CI) at all doses of the combination was below 1, indicating that Prx II antisense sensitized cisplatin-induced cell death. This synergism was also observed in the cells transfected with a Prx II antisense oligomer. Our present results, therefore, suggest that Prx II antisense would be a very good sensitizer for cisplatin, and that Prx II as a target for chemosensitizers constitutes a promising avenue for future research.
Yo
Young Do
YD
Korea University Cancer Institute, Korea University College of Medicine, Seoul 136-705, Korea.
Chung
Young Min
YM
Park
Jong Kuk
JK
Ahn
Chul Min
CM
Kim
Sung Kyu
SK
Kim
Hyung Jung
HJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005822:Genetic Vectors; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism*; D054464:Peroxiredoxins; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000975:Antioxidants; D016376:Oligonucleotides, Antisense; D010544:Peroxidases; D054464:Peroxiredoxins; D002945:Cisplatin