Mitomycin C cross-resistance induced by adriamycin in human ovarian cancer cells in vitro.
We prepared Adriamycin-resistant cancer cells by exposing an ovarian serous cystadenocarcinoma cell line to the drug. The resistant cells also showed cross-resistance to a wide variety of other compounds, including vincristine, vinblastine, actinomycin D, daunorubicin, mitomycin C and carboquone. Against vincristine, the cells showed a greater than 5,000-fold increase in resistance, far surpassing their resistance to the selection drug. The resistant cells displayed a decrease in intracellular Adriamycin content and an increase in the mRNA of the mdr-1 gene coding for P-glycoprotein, with no amplification of the DNA. In revertant cells, resistance to Adriamycin was lost, but that to mitomycin C was maintained. Adriamycin resistance was partially overcome by the addition of verapamil or cyclosporin A, but cross-resistance to mitomycin C was not influenced at all. These results strongly suggest that the resistance to mitomycin C observed in our Adriamycin-resistant cells was due to some other mechanism than that causing multidrug resistance.
Mizuno
K
K
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Japan.
Furuhashi
Y
Y
Maeda
O
O
Iwata
M
M
Misawa
T
T
Kawai
M
M
Kano
T
T
Tomoda
Y
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003524:Cyclosporins / Q000494:pharmacology; D003536:Cystadenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004273:DNA, Neoplasm / Q000378:metabolism; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014700:Verapamil / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003524:Cyclosporins; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D008937:Mitomycins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016685:Mitomycin; D014750:Vincristine; D004317:Doxorubicin; D014700:Verapamil