Induction of drug resistance to gold sodium thiomalate in a monocyte cell line, THP-1.
The expression of metallothionein, an intracellular heavy-metal-binding protein, and p-glycoprotein, an energy-dependent drug efflux pump, was examined to study the mechanism of cell resistance to gold sodium thiomalate (GST). THP-1, one of the monocyte-derived cell lines, was cultured for 6 months and resistance to 25 microg/ml of GST (GST-resistant cells) was thus induced. The GST-resistant cells were then cultured with bucillamine to examine the presence of cross-resistance. The intracellular GST concentration was examined by flameless atomic absorption spectroscopy. The cell viability was determined by the uptake of 3-4,5 dimethylthiazole-2,5 diphenyl tetrazolium bromide (MTT). The expression of p-glycoprotein was detected by Western blotting using monoclonal anti-p-glycoprotein antibody. The expression of metallothionein was detected using the indirect immunofluorescence technique. GST-resistant cells did not show any cross-resistance to bucillamine. The rate of cytoplasmic GST accumulation decreased in the GST-resistant cells, while the rate of GST efflux also decreased. The expression of p-glycoprotein in the GST-resistant cells was not significantly different from that in the cells not treated with GST. On the other hand, the GST-resistant cells showed a higher expression of metallothionein than cells not treated with GST. These findings suggest that the induced resistance to GST might partly be due to an induction of metallothionein.
Department of Clinical Immunology, Medical Institute of Bioregulation, Kyushu University, Beppu City, Oita, Japan.
Y
Y
Ichibangase
M
M
Yamamoto
M
M
Yasuda
N
N
Houki
M
M
Nobunaga
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D015153:Blotting, Western; D002460:Cell Line; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D003593:Cytoplasm / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D019084:Fluorescent Antibody Technique, Indirect; D006052:Gold Sodium Thiomalate / Q000032:analysis / Q000494:pharmacology*; D006801:Humans; D008668:Metallothionein / Q000032:analysis / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012680:Sensitivity and Specificity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006052:Gold Sodium Thiomalate; D008668:Metallothionein; D003545:Cysteine; C026535:bucillamine