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

Anticancer Res. 2009 Oct;29(10):4071-6.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / biosynthesis
  • ATP-Binding Cassette Transporters / genetics
  • Antimetabolites, Antineoplastic / pharmacology*
  • Blotting, Western
  • Cytarabine / pharmacology*
  • Daunorubicin / pharmacology
  • Drug Resistance, Neoplasm
  • Flow Cytometry
  • Gene Expression Regulation, Leukemic / drug effects*
  • Glutathione S-Transferase pi / biosynthesis
  • Glutathione S-Transferase pi / genetics
  • HL-60 Cells
  • Humans
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antimetabolites, Antineoplastic
  • Neoplasm Proteins
  • RNA, Messenger
  • Cytarabine
  • Glutathione S-Transferase pi
  • Daunorubicin