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.
Ichibangase
Y
Y
Department of Clinical Immunology, Medical Institute of Bioregulation, Kyushu University, Beppu City, Oita, Japan.
Yamamoto
M
M
Yasuda
M
M
Houki
N
N
Nobunaga
M
M
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