Abstract
Background:
Overexpression of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and glutathione-S-transferase pi (GSTpi) is associated with drug resistance in acute myeloid leukemia (AML). The short-term effects of drug exposure on their expression levels were investigated.
Materials and methods:
HL-60 cells and drug-resistant sublines were cultured with or without daunorubicin (DNR) and cytarabine (Ara-C). At several time-points the expression levels of P-gp, BCRP and GSTpi were determined.
Results:
After exposure to Ara-C, P-gp mRNA rapidly increased in all the cell lines. P-gp protein was detected in the sensitive cells after 8 h exposure to Ara-C. GSTpi mRNA increased in the resistant cells, but no change in BCRP mRNA was observed. Exposure to DNR revealed rapidly increased P-gp and GSTpi mRNA in the resistant cells.
Conclusion:
Ara-C rapidly increases P-gp mRNA and protein expression in sensitive and resistant cells, and GSTpi mRNA in resistant cells, in vitro. This may be of clinical importance during AML induction chemotherapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters / biosynthesis
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ATP-Binding Cassette Transporters / genetics
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Antimetabolites, Antineoplastic / pharmacology*
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Blotting, Western
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Cytarabine / pharmacology*
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Daunorubicin / pharmacology
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Drug Resistance, Neoplasm
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Flow Cytometry
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Gene Expression Regulation, Leukemic / drug effects*
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Glutathione S-Transferase pi / biosynthesis
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Glutathione S-Transferase pi / genetics
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HL-60 Cells
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Humans
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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RNA, Messenger / biosynthesis*
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RNA, Messenger / genetics
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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ABCG2 protein, human
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters
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Antimetabolites, Antineoplastic
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Neoplasm Proteins
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RNA, Messenger
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Cytarabine
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Glutathione S-Transferase pi
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Daunorubicin