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.
School of Health and Medical Sciences, Orebro University, Orebro, Sweden. malin.prenkert@orebroll.se
Malin
M
Prenkert
Bertil
B
Uggla
Elisabet
E
Tina
Ulf
U
Tidefelt
Hilja
H
Strid
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