Rapid induction of P-glycoprotein mRNA and protein expression by cytarabine in HL-60 cells.
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.


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.


CONCLUSIONS
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.
Prenkert
Malin
M
School of Health and Medical Sciences, Orebro University, Orebro, Sweden. malin.prenkert@orebroll.se
Uggla
Bertil
B
Tina
Elisabet
E
Tidefelt
Ulf
U
Strid
Hilja
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D015153:Blotting, Western; D003561:Cytarabine / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D051549:Glutathione S-Transferase pi / Q000096:biosynthesis / Q000235:genetics; D018922:HL-60 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000964:Antimetabolites, Antineoplastic; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D003561:Cytarabine; D051549:Glutathione S-Transferase pi; D003630:Daunorubicin