Mechanism of interaction between cisplatin and human recombinant interferon gamma in human ovarian-cancer cell lines.
Human ovarian carcinoma cells (2008 and its cisplatin-resistant sub-line 2008/C13*) were sensitized to cisplatin by treatment with human recombinant gamma interferon (IFN gamma). IFN gamma produced no significant change in the uptake of CDDP. Exposure of 2008 and 2008/C13* cells to IFN gamma resulted in a time-dependent decrease of cellular glutathione and total glutathione-S-transferase activity, principally the pi isoform. By contrast, the treatment of 2008 and 2008/C13* cell lines with IFN gamma induced rather than suppressed metallothionein IIA mRNA levels. IFN gamma changed neither the formation of total platinum-DNA adducts, nor DNA repair. A significant decrease in c-erbB-2 expression was observed both in sensitive and in resistant cell lines after treatment with IFN gamma, and this decrease was dose-dependent. Our results indicate that the mechanism of IFN gamma-induced sensitization in human ovarian-cancer cell lines is multifactorial.
Nehmé
A
A
Groupe de Pharmacologie Expérimentale des Médicaments Anticancéreux, Centre Claudius Regaud, Toulouse, France.
Albin
N
N
Caliaro
M J
MJ
Guichard
S
S
Jozan
S
S
Julia
A M
AM
Bugat
R
R
Canal
P
P
D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D015870:Gene Expression; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008668:Metallothionein / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D008668:Metallothionein; D002945:Cisplatin