Cisplatin resistance is associated with reduced interferon-gamma-sensitivity and increased HER-2 expression in cultured ovarian carcinoma cells.
In ovarian carcinoma cells, the combination of interferon-gamma (IFN-gamma) and cisplatin (cDDP) has been reported to result in a synergistic amplification of antiproliferative activity. To assess whether IFN-gamma may also prevent the occurrence of cisplatin resistance, the human ovarian carcinoma cell line HTB-77 was treated repeatedly in an intermittent fashion with either cisplatin alone (HTB-77cDDP) or cisplatin plus IFN-gamma (HTB-77cDDP + IFN). After 8 months of treatment, both new lines (HTB-77cDDP or HTB-77cDDP + IFN) were found to be three times more resistant to cisplatin than the wild-type cells (HTB-77wt). IFN-gamma could not prevent the development of cisplatin resistance. Interestingly, both HTB-77cDDP and HTB-77cDDP + IFN cells were also less IFN-gamma sensitive than the parental line. Both cisplatin-resistant lines expressed p185HER-2 and HER-2 mRNA at a higher concentration than the HTB-77wt cells. IFN-gamma was in all three HTB-77 cell lines able to suppress the HER-2 message and its encoded protein. The expression of IFN-gamma-induced antigens, namely CA-125 and class II antigens of the major histocompatibility complex (HLA-DR), was markedly augmented by IFN-gamma in all three lines, whereby the most prominent effect was seen in HTB-77cDDP and HTB-77cDDP + IFN.
Marth
C
C
Department of Obstetrics and Gynaecology, University Hospital, Innsbruck, Austria.
Widschwendter
M
M
Kaern
J
J
Jørgensen
N P
NP
Windbichler
G
G
Zeimet
A G
AG
Tropé
C
C
Daxenbichler
G
G
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D018734:Genes, erbB-2; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006684:HLA-DR Antigens; D007371:Interferon-gamma; D002945:Cisplatin